OncoImmunology
ISSN: (Print) 2162-402X (Online) Journal homepage: http://www.tandfonline.com/loi/koni20
Multifaceted antitumor responses to activating anti-CD40 antibody therapy combined with immunomodulatory or targeted agents Jonathan M Weiss & Robert H Wiltout To cite this article: Jonathan M Weiss & Robert H Wiltout (2014) Multifaceted antitumor responses to activating anti-CD40 antibody therapy combined with immunomodulatory or targeted agents, OncoImmunology, 3:8, e954483, DOI: 10.4161/21624011.2014.954483 To link to this article: http://dx.doi.org/10.4161/21624011.2014.954483
Published online: 14 Nov 2014.
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Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=koni20 Download by: [63.235.180.46]
Date: 05 November 2015, At: 15:10
AUTHOR'S VIEW OncoImmunology 3:8, e954483; August 1, 2014; © 2014 Taylor & Francis Group, LLC
Multifaceted antitumor responses to activating anti-CD40 antibody therapy combined with immunomodulatory or targeted agents Jonathan M Weiss and Robert H Wiltout* Cancer and Inflammation Program; National Cancer Institute; Frederick, MD USA
Keywords: biomarkers, immunostimulation, immunotherapy, inflammation, targets, therapeutic antibodies
Downloaded by [63.235.180.46] at 15:10 05 November 2015
Therapeutic targeting of the CD40 pathway may be efficacious for cancer treatment. Accumulating evidence suggests synergistic and unique antitumor responses may be achieved using CD40-based therapies in combination with other immunomodulators or targeted agents.
CD40-CD40 ligand interactions constitute a critical co-stimulatory pathway for promoting antigen presenting cell (APC) activation and CD8C T cell-mediated protective immunity to cancer. Agonistic antibodies to CD40 (aCD40) represent promising therapeutic options to generate antitumor immunity by both direct and indirect mechanisms. We, and others, have shown that aCD40 mediates antitumor responses indirectly by stimulating APC activation, as well as directly by triggering CD40-positive tumor cells to produce cytokines,1 express the death receptor Fas and induce Fas-dependent tumor cell apoptosis.2 Upregulated expression of CD40 has been noted in nephritis and other renal diseases. However, until recently no correlation between renal cell carcinoma (RCC)-associated CD40 expression and patient outcome had been described. Since ligation of tumor-associated CD40 has direct anticancer effects, we speculated that CD40 expression might have prognostic value in RCC. In our retrospective study, we found that tumor-associated CD40 expression was highest among long-term survivors (>8 year follow-up time).3 In contrast, short-term survivors (
ISSN: (Print) 2162-402X (Online) Journal homepage: http://www.tandfonline.com/loi/koni20
Multifaceted antitumor responses to activating anti-CD40 antibody therapy combined with immunomodulatory or targeted agents Jonathan M Weiss & Robert H Wiltout To cite this article: Jonathan M Weiss & Robert H Wiltout (2014) Multifaceted antitumor responses to activating anti-CD40 antibody therapy combined with immunomodulatory or targeted agents, OncoImmunology, 3:8, e954483, DOI: 10.4161/21624011.2014.954483 To link to this article: http://dx.doi.org/10.4161/21624011.2014.954483
Published online: 14 Nov 2014.
Submit your article to this journal
Article views: 26
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=koni20 Download by: [63.235.180.46]
Date: 05 November 2015, At: 15:10
AUTHOR'S VIEW OncoImmunology 3:8, e954483; August 1, 2014; © 2014 Taylor & Francis Group, LLC
Multifaceted antitumor responses to activating anti-CD40 antibody therapy combined with immunomodulatory or targeted agents Jonathan M Weiss and Robert H Wiltout* Cancer and Inflammation Program; National Cancer Institute; Frederick, MD USA
Keywords: biomarkers, immunostimulation, immunotherapy, inflammation, targets, therapeutic antibodies
Downloaded by [63.235.180.46] at 15:10 05 November 2015
Therapeutic targeting of the CD40 pathway may be efficacious for cancer treatment. Accumulating evidence suggests synergistic and unique antitumor responses may be achieved using CD40-based therapies in combination with other immunomodulators or targeted agents.
CD40-CD40 ligand interactions constitute a critical co-stimulatory pathway for promoting antigen presenting cell (APC) activation and CD8C T cell-mediated protective immunity to cancer. Agonistic antibodies to CD40 (aCD40) represent promising therapeutic options to generate antitumor immunity by both direct and indirect mechanisms. We, and others, have shown that aCD40 mediates antitumor responses indirectly by stimulating APC activation, as well as directly by triggering CD40-positive tumor cells to produce cytokines,1 express the death receptor Fas and induce Fas-dependent tumor cell apoptosis.2 Upregulated expression of CD40 has been noted in nephritis and other renal diseases. However, until recently no correlation between renal cell carcinoma (RCC)-associated CD40 expression and patient outcome had been described. Since ligation of tumor-associated CD40 has direct anticancer effects, we speculated that CD40 expression might have prognostic value in RCC. In our retrospective study, we found that tumor-associated CD40 expression was highest among long-term survivors (>8 year follow-up time).3 In contrast, short-term survivors (
