Conference Report groups represents an up-to-date evaluation of the state of the art in this area In particular, the chapters on the Hepadnavlridae, the influenza viruses and Herpes simplex virus are highly pertinent and the current situation w~thin these groups is comprehensively described The overview provided by the first eight chapters of the book is a much more general exposition on selected aspects of viral antlgenlcity, with both fundamental and more applied topics represented They not only provide a perspective on the subject, but also hlghhght a number of problem areas currently undergoing detailed research investigation However,
one or two chapters seem slightly out of context here, and although it is appreciated that the editors are attempting to coalesce under one cover two quite different strands of approach, namely the antigenic structure of infecting virus and the detailed aspects of the immune response provoked, that should come together and be understood if viral diseases are to be controlled by vaccines developed using this new technology, it seems that the final impact of this section of the book is not quite the sum of its parts Nevertheless, the book has a great deal to offer, it is highly presentable
and comprehensively referenced, and, although like most other books of this nature it will tend to date, gives an excellent current perspective of the achievements so far made in understanding viral antigen fine structure, and points out the directions being followed in attempts to harness this knowledge towards the development of safer viral vaccines targeted towards ehclting only the required, and not unwanted or irrelevant, immune responses
R Jennings Sheffteld
Conference Report Workshop on the regulation of biologicals 20--22 March 1991, NIH, Washington, DC, USA The concluding remarks of the 'International Workshop on Continuous Lines Current Issues' recalled that the late Hope Hopps called for the expansion of the "rational scientific framework to build regulatory discussions' Since that call went out, the regulatory authorities have required 'good science' as the basis on which new biological products will be judged worthy of a 'hcence to manufacture and sell" But is rational science enough 9 Knowledge of all sorts can be obtained and tested for soundness but if it is of little lelet'ame or creates confusion and obfuscation, it may not be of benefit In short, we may have excellent tests for sequencing genomes, identifying chromosomes, rescuing retroviruses and giving cancers to nude mice, but do their results further our objective of putting safe and efficacious prophylactics and therapeutics into the market place 9 If not, such knowledge may be regressive and a hindrance to progress At this workshop, we heard much of the 'concerns' and problems' of the agency, and of the 'issues' that occupy their attention but we did not hear the word 'relevance' The new scientific data on the ability to make pseudotype retroviruses and to rescue infectious retroviruses from cells which had defective retroviruses on board was discussed at length but its relevance was httle considered Are such viruses pathogenic 9
0264-410X/91/090693-03 © 1991Butterworth-Hememann Ltd
The only relevant data quoted concerned the injection of 107 particles of an amphotroplc retrovlrus into monkeys which, although they showed a vlraemla, did not show signs of disease (This experiment is still in its early stages and the long-term effects of this kind of treatment are eagerly awaited) It was also mentioned that when humans encounter infectious retrovlruses they are speedily dealt with by the complement system These observaUons need not lull us into complacency but should put into perspective the intensive activities which seek to both remove and inactivate retroviruses in final product streams Surely, the undetectable levels of such materials can hardly be considered to pose a problem We are, however, conditioned by the situation which led to the Infection of haemophlhacs with HIV by contaminated Factor VIII preparations The lessons we have learned from the use of whole animal matermls in the past have clearly been forgotten In the recent past humans have been infected with syphilis when using human pustular material for smallpox vaccinations or with hepatitis, using human serum albumin as a yellow fever vaccine stabilizer or with prions, when making either human growth hormone from pituitary tissues or when performing corneal transplants There is a clear need for extra precautions when dealing with products from a human
source Getting infections from animals seems that much more difficult After all, inoculations with avian leucosls retrovlrus via yellow fever and influenza vaccines had no apparent deleterious effects and we rejected Simian SV40 as inactivated polio vaccine (the SV40 can survive the reactivation procedure) We ingested the same virus in live polio vaccines, again without apparent effect This Is not to suggest that we should deliberately and knowingly reject and ingest all manner of infectious r,aaterials ad hhitum, but rather that when we think we know what we are doing then we should have the confidence to make available the fruits of our creativity to suffering individuals without spending, perhaps, hundreds of millions of dollars and tens of years to prove what we already know This conference had four main areas at focus cell line characterization, genetic stability and biochemical assays, retrovirus biology and vahdatlon procedures The 425 conferees from 25 countries heard over 40 papers and spent 2 5 days listening to new data and considering how it should relate to their work All parties to the contract of putting a biological Into the market place must have 'confidence' and 'feelings of comfort' At present we focus on removing all potential problem materials from the product without first ascertaining that such materials are a problem In our present state of ignorance ~t is prudent
Vacc,ne, Vol 9, September 1991 693
Conference Report to be assiduous about this aspect of the final product When we understand the ploblems better we should be able to relax procedures and decrease the time to get new products to the patients
Cell characterization Having 'fully' characterized the master cell bank (MCB), the working cell bank needs to be estabhshed and provision should be made to examine the cells at the end of the process Authenticity, identity and quality control are key requirements It must also be established that contaminants are absent or that the contaminants that are known to be present do not constitute a threat Clearly, Karyology is of little value in chromosomally unstable cell lines (hybrldomas) but lsoenzyme analysis could be a substitute, the nature, type and yield of the specific monoclonal could always be used as a cell line characterizing parameter PCR and D N A fingerprinting hold promise but they have yet to become routine methods of choice in th~s area as they both need extensive validation before becoming acceptable The main area of contention was in the need for the testing of tumorigenic cell lines for their tumorigenicity in nude mice or equivalent animal systems Although It may be reassuring to know that you still have what you thought you had, there are surely simpler and less expensive methods that would give the same degree of assurance Colony formation in soft agar and preclpltablhty by lectlns are two of a potential battery of possible m t tt~o tests Novel procedures will be needed when the TIL cell systems become more widespread These are presently treated on a case [Individual treatment) by case basis but with experience, principles wdl no doubt emerge which will expedite matters The use of Lepldopteran cell lines seems promising these do not seem to harbour viral contaminants but on the other hand do not generally effect an appropriate posttranslaUonal processing scheme
Genetic and biochemical facets The question of the sufficiency of the biochemical characterization of the product was raised Could peptlde maps. which seem to be a more sensitive method than restriction enzyme mapping of nucleic acids, be used as a product identifier 9 Such a technique would not detect a 5% level of contamination by a similar protein, but then, what method would '~ Also the characterization of the carbohydrate momty of a glycoproteln while considered necessary to tie down the range of glycoforms, does not provide a complete description of the product Immunological assays could also be used to detect very low levels of contamlnatlng
694
Vaccine, Vol 9, September 1991
proteins but such systems could be difficult to set up and validate These requirements are made in order to ascertain the 'consistency' of production There was, however, little attempt to define the meaning of this term, or how much lahtude should be regarded as reasonable and how this would vary between product materials With regard to the gene inserts, the copy number could vary throughout a protracted run without a change in the rate of generation of product or In the quahty of that material Indeed, the posltlOn in which the gene is s~tuated in the chromosome does not seem to influence the product quahty or quantity While it may be practicable to relsolate bacterial plasmlds and show, by sequencing, that they have not changed in the process it is of less value to do this in animal cell systems Th~s is a consequence of hawng to select a single gene for amplification and as such this may not be representative of the whole population situation It ~s hoped that the retsolatlon of the inserted gene would not be a regular requirement for process validation There would still be a place for bloassays and the lmphcatlons of long term cultures have to be further addressed and techmques to monitor and regulate such operations need to be put in place
Retroviruses and retrovirus vectors It is clear that the downstream stages should both remove and inactivate retrovIruses However, the addltlveness of the log reduction values needs to be effected with care and is suspect when multiples of the same unit operation are used as opposed to a series of operations each of which has a different way of rather removing or Inactivating the virus It should also be recogmzed that each retrov~rus may respond to the removal/ inactivation procedures differently m a manner affected by the nature of the surrounding environment, including the effects on the process stream of the preceding operations Some risk has been attributed to the mouse human hybrldomas because, although there is little fear of retrovlruses from the human partner, there are retrovlrus receptors on the human cells which may promote retrovirus entry into the cells Other cell lines such as the C H O cells pose less of a risk as they tend to have the non-infectious A-type particles Detection of Infectious particles is still difficult and Involves the use of cocultivation or the use of the S + / L - cell hne for the amphotroplc and xenotroplc wruses This latter assay based on the observation of loci in monolayers of cells is difficult for routine operations as infected cultures need to be Interpreted with care and experience
Other assays for retrovzruses were also discussed Electron microscopy, while important for investigating new types of cell cultures, is of little value in routine observaUons of standard cell lines Similarly, the use of the methods to detect the enzyme reverse transcrlptase has to be effected with care as the enzyme activity is dependent on the availability of divalent Ions (Mg 2+ and/or Mn 2+) and the relative concentrations of these materials m relation to the other ions in the env,ronment ~s crumal to the measurement of the enzyme activity PCR has been suggested as a method to detect viruses but for th~s method Jt Is necessary to know for which virus one is testing Methods involving the ad&tlon of known primer sequences with llgatlng enzymes which could fish for all D N A molecules present seem to present genetic engineers with problems which have yet to be surmounted An alternative approach ma2¢ Involve looking for sequences in the genes for rather DNA or RNA polymerase which might be conserved in all viruses Whichever assay is used, it is essential to have well trained and reliable personnel effectlng the experiments The use of retrovlrus vectors for correcting somatic gene deficiencies or, when carrying anti-sense nucleic acid, for down-regulating endogenous genes has been given attention When such vectors are positioned in lymphocytes It is possible that the insertion of the vector could change the oncogemclty of the treated cell This could arrwe from the insertion of the vector so that cellular oncogenes are activated or suppressor genes are inactivated or housekeeping genes are changed in their expression It is even possible that if an oncogenlcally transformed lymphocyte were inoculated into a patient with a functioning immune system the latter would take care of the aberrant Interloper With lmmunosuppressed patients, however, greater caution would be in order
Validation methods Developments m filtration techniques have lead to the 0 04/tin filter which is effective down to 0 91 l~m test particles While the system has not been extensively tested with viruses, it would seem likely that the larger viruses would be separated out with such a membrane but that smaller viruses (plcorna- and parvoviruses) would penetrate this system The choice of a spiking virus is also a possible cause for concern Duck hepatitis virus, while con,cenlently not a human pathogen, might not be an apposite model for human hepatms B virus The problem of vtrus-hke agents such as scraple and bovine spongltorm encephalopathy was raised and In the absence of sound methods of detection it was held that the epldemlology of these
Conference Report agents, particularly the principally neurological location of the infectious materials, suggests that patients are unhkely to become infected when we use the serum from possibly infected ammals and purify the product material so as to remove most. if not all, the proteins which have been introduced mto the process by the use of bowne serum Conclusions Regulatory agencies, companies, umversltmS and government research laboratories have jointly advanced the knowledge and understanding of the factors
imphclt m making safe and efficacious products for the prevention and treatment of human dzsease This is achmved by the application of great care and effort not only to prevent known hazards but also to counter conceptuahzed dangers which collateral work has indicated are possible Much needs to be done to determine the actual nature of the risks whmh are faced when using bmlogmals derwed from cell hnes whose genomes contain hundreds or thousands of copies of retrovirus-assocmted sequences and when vlrus-hke particles can be observed in cell cultures Addmonally, the requirement for relevance m the tests whmh are
Second International C o n f e r e n c e on Human Antibodies and Hybridomas
MARCH 24-2fb 1 9 9 2 Queens' College Cambridge, UK PROGRAM CHAIRMAN
done should be applied with greater ngour m order to bring down the proh~bmvely high costs of introducing products to the market place, thus preventing valuable bmlogmals from exerting their beneficial effects for many years after the discovery of their potentml apphcatmn This meeting affirmed the continuing evaluatmn and regulatmn of bmlogmals with an emphasis on making practicable what Is of benefit to socmty
R.E. Spier Umverslty of Surrey, Gutldford, Surrey, UK
SPONSOR
The journal HUMAN ANTIBODIES AND HYBRIDOMAS
Mark C. Glassy, PhD Sci-Clone, Inc. San Diego, CA, USA
PROGRAM
SUBMISSION
Following the r e s o u n d i n g success of the First I n t e r n a t i o n a l Conference, held in Orlando, Florida, in April 1990, ButterworthH e i n e m a n n is pleased to a n n o u n c e that the Second I n t e r n a t i o n a l Conference on H u m a n Antlbodms a n d Hybrldomas will take place in picturesque Cambridge, England, in the spring of 1992 The scmntific program wdl conmst of keynote lectures by invited speakers, c o n t r i b u t e d papers, a n d poster p r e s e n t a t i o n s emphasizing all aspects of h u m a n hybrldoma and a n t i b o d y technology
Submission of papers for oral p r e s e n t a t i o n is now invited Acceptance will be decided by the Conference Advisory Board on the grounds of intrinsic merit a n d relevance to the main t h e m e s of the c o n f e r e n c e Poster p r e s e n t a t i o n s will also he considered Prospective a u t h o r s of papers a n d posters are requested to s u b m i t a n abstract of no more t h a n 250 words The style should be similar to t h a t of t h e a n n u a l FASEB meetings Use CAPITALS for PAPER TITLE, a u t h o r s ' n a m e s (speakers u n d e r l i n e d ) a n d addresses should be m capital a n d lower case Begin headings from left margin Use single spacing C l o s i n g d a t e f o r a b s t r a c t s is O c t o b e r 15, 1991. Contact Susan L Patterson Butterworth-Hememann 80 Montvale Avenue Stoneham, MA 02180, USA Telephone (617) 438-8464, ext 234 or 303 FAX (617) 279-4851
I"~U
TT
WE
I
E R WO N
E
M
A
CONFERENCES WHERE PROFESSIONALS MEET
RT
H
N
N
OF PAPERS AND POSTERS
Vaccine, Vol 9, September 1991 695
one or two chapters seem slightly out of context here, and although it is appreciated that the editors are attempting to coalesce under one cover two quite different strands of approach, namely the antigenic structure of infecting virus and the detailed aspects of the immune response provoked, that should come together and be understood if viral diseases are to be controlled by vaccines developed using this new technology, it seems that the final impact of this section of the book is not quite the sum of its parts Nevertheless, the book has a great deal to offer, it is highly presentable
and comprehensively referenced, and, although like most other books of this nature it will tend to date, gives an excellent current perspective of the achievements so far made in understanding viral antigen fine structure, and points out the directions being followed in attempts to harness this knowledge towards the development of safer viral vaccines targeted towards ehclting only the required, and not unwanted or irrelevant, immune responses
R Jennings Sheffteld
Conference Report Workshop on the regulation of biologicals 20--22 March 1991, NIH, Washington, DC, USA The concluding remarks of the 'International Workshop on Continuous Lines Current Issues' recalled that the late Hope Hopps called for the expansion of the "rational scientific framework to build regulatory discussions' Since that call went out, the regulatory authorities have required 'good science' as the basis on which new biological products will be judged worthy of a 'hcence to manufacture and sell" But is rational science enough 9 Knowledge of all sorts can be obtained and tested for soundness but if it is of little lelet'ame or creates confusion and obfuscation, it may not be of benefit In short, we may have excellent tests for sequencing genomes, identifying chromosomes, rescuing retroviruses and giving cancers to nude mice, but do their results further our objective of putting safe and efficacious prophylactics and therapeutics into the market place 9 If not, such knowledge may be regressive and a hindrance to progress At this workshop, we heard much of the 'concerns' and problems' of the agency, and of the 'issues' that occupy their attention but we did not hear the word 'relevance' The new scientific data on the ability to make pseudotype retroviruses and to rescue infectious retroviruses from cells which had defective retroviruses on board was discussed at length but its relevance was httle considered Are such viruses pathogenic 9
0264-410X/91/090693-03 © 1991Butterworth-Hememann Ltd
The only relevant data quoted concerned the injection of 107 particles of an amphotroplc retrovlrus into monkeys which, although they showed a vlraemla, did not show signs of disease (This experiment is still in its early stages and the long-term effects of this kind of treatment are eagerly awaited) It was also mentioned that when humans encounter infectious retrovlruses they are speedily dealt with by the complement system These observaUons need not lull us into complacency but should put into perspective the intensive activities which seek to both remove and inactivate retroviruses in final product streams Surely, the undetectable levels of such materials can hardly be considered to pose a problem We are, however, conditioned by the situation which led to the Infection of haemophlhacs with HIV by contaminated Factor VIII preparations The lessons we have learned from the use of whole animal matermls in the past have clearly been forgotten In the recent past humans have been infected with syphilis when using human pustular material for smallpox vaccinations or with hepatitis, using human serum albumin as a yellow fever vaccine stabilizer or with prions, when making either human growth hormone from pituitary tissues or when performing corneal transplants There is a clear need for extra precautions when dealing with products from a human
source Getting infections from animals seems that much more difficult After all, inoculations with avian leucosls retrovlrus via yellow fever and influenza vaccines had no apparent deleterious effects and we rejected Simian SV40 as inactivated polio vaccine (the SV40 can survive the reactivation procedure) We ingested the same virus in live polio vaccines, again without apparent effect This Is not to suggest that we should deliberately and knowingly reject and ingest all manner of infectious r,aaterials ad hhitum, but rather that when we think we know what we are doing then we should have the confidence to make available the fruits of our creativity to suffering individuals without spending, perhaps, hundreds of millions of dollars and tens of years to prove what we already know This conference had four main areas at focus cell line characterization, genetic stability and biochemical assays, retrovirus biology and vahdatlon procedures The 425 conferees from 25 countries heard over 40 papers and spent 2 5 days listening to new data and considering how it should relate to their work All parties to the contract of putting a biological Into the market place must have 'confidence' and 'feelings of comfort' At present we focus on removing all potential problem materials from the product without first ascertaining that such materials are a problem In our present state of ignorance ~t is prudent
Vacc,ne, Vol 9, September 1991 693
Conference Report to be assiduous about this aspect of the final product When we understand the ploblems better we should be able to relax procedures and decrease the time to get new products to the patients
Cell characterization Having 'fully' characterized the master cell bank (MCB), the working cell bank needs to be estabhshed and provision should be made to examine the cells at the end of the process Authenticity, identity and quality control are key requirements It must also be established that contaminants are absent or that the contaminants that are known to be present do not constitute a threat Clearly, Karyology is of little value in chromosomally unstable cell lines (hybrldomas) but lsoenzyme analysis could be a substitute, the nature, type and yield of the specific monoclonal could always be used as a cell line characterizing parameter PCR and D N A fingerprinting hold promise but they have yet to become routine methods of choice in th~s area as they both need extensive validation before becoming acceptable The main area of contention was in the need for the testing of tumorigenic cell lines for their tumorigenicity in nude mice or equivalent animal systems Although It may be reassuring to know that you still have what you thought you had, there are surely simpler and less expensive methods that would give the same degree of assurance Colony formation in soft agar and preclpltablhty by lectlns are two of a potential battery of possible m t tt~o tests Novel procedures will be needed when the TIL cell systems become more widespread These are presently treated on a case [Individual treatment) by case basis but with experience, principles wdl no doubt emerge which will expedite matters The use of Lepldopteran cell lines seems promising these do not seem to harbour viral contaminants but on the other hand do not generally effect an appropriate posttranslaUonal processing scheme
Genetic and biochemical facets The question of the sufficiency of the biochemical characterization of the product was raised Could peptlde maps. which seem to be a more sensitive method than restriction enzyme mapping of nucleic acids, be used as a product identifier 9 Such a technique would not detect a 5% level of contamination by a similar protein, but then, what method would '~ Also the characterization of the carbohydrate momty of a glycoproteln while considered necessary to tie down the range of glycoforms, does not provide a complete description of the product Immunological assays could also be used to detect very low levels of contamlnatlng
694
Vaccine, Vol 9, September 1991
proteins but such systems could be difficult to set up and validate These requirements are made in order to ascertain the 'consistency' of production There was, however, little attempt to define the meaning of this term, or how much lahtude should be regarded as reasonable and how this would vary between product materials With regard to the gene inserts, the copy number could vary throughout a protracted run without a change in the rate of generation of product or In the quahty of that material Indeed, the posltlOn in which the gene is s~tuated in the chromosome does not seem to influence the product quahty or quantity While it may be practicable to relsolate bacterial plasmlds and show, by sequencing, that they have not changed in the process it is of less value to do this in animal cell systems Th~s is a consequence of hawng to select a single gene for amplification and as such this may not be representative of the whole population situation It ~s hoped that the retsolatlon of the inserted gene would not be a regular requirement for process validation There would still be a place for bloassays and the lmphcatlons of long term cultures have to be further addressed and techmques to monitor and regulate such operations need to be put in place
Retroviruses and retrovirus vectors It is clear that the downstream stages should both remove and inactivate retrovIruses However, the addltlveness of the log reduction values needs to be effected with care and is suspect when multiples of the same unit operation are used as opposed to a series of operations each of which has a different way of rather removing or Inactivating the virus It should also be recogmzed that each retrov~rus may respond to the removal/ inactivation procedures differently m a manner affected by the nature of the surrounding environment, including the effects on the process stream of the preceding operations Some risk has been attributed to the mouse human hybrldomas because, although there is little fear of retrovlruses from the human partner, there are retrovlrus receptors on the human cells which may promote retrovirus entry into the cells Other cell lines such as the C H O cells pose less of a risk as they tend to have the non-infectious A-type particles Detection of Infectious particles is still difficult and Involves the use of cocultivation or the use of the S + / L - cell hne for the amphotroplc and xenotroplc wruses This latter assay based on the observation of loci in monolayers of cells is difficult for routine operations as infected cultures need to be Interpreted with care and experience
Other assays for retrovzruses were also discussed Electron microscopy, while important for investigating new types of cell cultures, is of little value in routine observaUons of standard cell lines Similarly, the use of the methods to detect the enzyme reverse transcrlptase has to be effected with care as the enzyme activity is dependent on the availability of divalent Ions (Mg 2+ and/or Mn 2+) and the relative concentrations of these materials m relation to the other ions in the env,ronment ~s crumal to the measurement of the enzyme activity PCR has been suggested as a method to detect viruses but for th~s method Jt Is necessary to know for which virus one is testing Methods involving the ad&tlon of known primer sequences with llgatlng enzymes which could fish for all D N A molecules present seem to present genetic engineers with problems which have yet to be surmounted An alternative approach ma2¢ Involve looking for sequences in the genes for rather DNA or RNA polymerase which might be conserved in all viruses Whichever assay is used, it is essential to have well trained and reliable personnel effectlng the experiments The use of retrovlrus vectors for correcting somatic gene deficiencies or, when carrying anti-sense nucleic acid, for down-regulating endogenous genes has been given attention When such vectors are positioned in lymphocytes It is possible that the insertion of the vector could change the oncogemclty of the treated cell This could arrwe from the insertion of the vector so that cellular oncogenes are activated or suppressor genes are inactivated or housekeeping genes are changed in their expression It is even possible that if an oncogenlcally transformed lymphocyte were inoculated into a patient with a functioning immune system the latter would take care of the aberrant Interloper With lmmunosuppressed patients, however, greater caution would be in order
Validation methods Developments m filtration techniques have lead to the 0 04/tin filter which is effective down to 0 91 l~m test particles While the system has not been extensively tested with viruses, it would seem likely that the larger viruses would be separated out with such a membrane but that smaller viruses (plcorna- and parvoviruses) would penetrate this system The choice of a spiking virus is also a possible cause for concern Duck hepatitis virus, while con,cenlently not a human pathogen, might not be an apposite model for human hepatms B virus The problem of vtrus-hke agents such as scraple and bovine spongltorm encephalopathy was raised and In the absence of sound methods of detection it was held that the epldemlology of these
Conference Report agents, particularly the principally neurological location of the infectious materials, suggests that patients are unhkely to become infected when we use the serum from possibly infected ammals and purify the product material so as to remove most. if not all, the proteins which have been introduced mto the process by the use of bowne serum Conclusions Regulatory agencies, companies, umversltmS and government research laboratories have jointly advanced the knowledge and understanding of the factors
imphclt m making safe and efficacious products for the prevention and treatment of human dzsease This is achmved by the application of great care and effort not only to prevent known hazards but also to counter conceptuahzed dangers which collateral work has indicated are possible Much needs to be done to determine the actual nature of the risks whmh are faced when using bmlogmals derwed from cell hnes whose genomes contain hundreds or thousands of copies of retrovirus-assocmted sequences and when vlrus-hke particles can be observed in cell cultures Addmonally, the requirement for relevance m the tests whmh are
Second International C o n f e r e n c e on Human Antibodies and Hybridomas
MARCH 24-2fb 1 9 9 2 Queens' College Cambridge, UK PROGRAM CHAIRMAN
done should be applied with greater ngour m order to bring down the proh~bmvely high costs of introducing products to the market place, thus preventing valuable bmlogmals from exerting their beneficial effects for many years after the discovery of their potentml apphcatmn This meeting affirmed the continuing evaluatmn and regulatmn of bmlogmals with an emphasis on making practicable what Is of benefit to socmty
R.E. Spier Umverslty of Surrey, Gutldford, Surrey, UK
SPONSOR
The journal HUMAN ANTIBODIES AND HYBRIDOMAS
Mark C. Glassy, PhD Sci-Clone, Inc. San Diego, CA, USA
PROGRAM
SUBMISSION
Following the r e s o u n d i n g success of the First I n t e r n a t i o n a l Conference, held in Orlando, Florida, in April 1990, ButterworthH e i n e m a n n is pleased to a n n o u n c e that the Second I n t e r n a t i o n a l Conference on H u m a n Antlbodms a n d Hybrldomas will take place in picturesque Cambridge, England, in the spring of 1992 The scmntific program wdl conmst of keynote lectures by invited speakers, c o n t r i b u t e d papers, a n d poster p r e s e n t a t i o n s emphasizing all aspects of h u m a n hybrldoma and a n t i b o d y technology
Submission of papers for oral p r e s e n t a t i o n is now invited Acceptance will be decided by the Conference Advisory Board on the grounds of intrinsic merit a n d relevance to the main t h e m e s of the c o n f e r e n c e Poster p r e s e n t a t i o n s will also he considered Prospective a u t h o r s of papers a n d posters are requested to s u b m i t a n abstract of no more t h a n 250 words The style should be similar to t h a t of t h e a n n u a l FASEB meetings Use CAPITALS for PAPER TITLE, a u t h o r s ' n a m e s (speakers u n d e r l i n e d ) a n d addresses should be m capital a n d lower case Begin headings from left margin Use single spacing C l o s i n g d a t e f o r a b s t r a c t s is O c t o b e r 15, 1991. Contact Susan L Patterson Butterworth-Hememann 80 Montvale Avenue Stoneham, MA 02180, USA Telephone (617) 438-8464, ext 234 or 303 FAX (617) 279-4851
I"~U
TT
WE
I
E R WO N
E
M
A
CONFERENCES WHERE PROFESSIONALS MEET
RT
H
N
N
OF PAPERS AND POSTERS
Vaccine, Vol 9, September 1991 695
