American Association for Cancer Research
10780432ccr120979-sup-fig3.pdf (174.94 kB)

Supplementary Figure 3 from A Novel Therapeutic Regimen to Eradicate Established Solid Tumors with an Effective Induction of Tumor-Specific Immunity

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journal contribution
posted on 2023-03-31, 17:44 authored by James R. Tysome, Xiaozhu Li, Shengdian Wang, Pengju Wang, Dongling Gao, Pan Du, Dong Chen, Rathi Gangeswaran, Louisa S. Chard, Ming Yuan, Ghassan Alusi, Nicholas R. Lemoine, Yaohe Wang

PDF file - 174K, Efficiency of the monoclonal antibody 4F11 in depleting CD3+ T-cells in vivo



Purpose: The efficacy of oncolytic viruses depends on multiple actions including direct tumor lysis, modulation of tumor perfusion, and stimulation of tumor-directed immune responses. In this study, we investigated whether a sequential combination of immunologically distinct viruses might enhance antitumor efficacy through the induction of tumor-specific immunity and circumvention or mitigation of antiviral immune responses.Experimental Design: The Syrian hamster as an immune-competent model that supports replication of both adenovirus and vaccinia virus was evaluated in vitro and in vivo. The antitumor efficacy of either virus alone or sequential combination of the two viruses was examined in pancreatic and kidney cancer models. The functional mechanism of the regimen developed here was investigated by histopathology, immunohistochemistry staining, CTL assay, and T-cell depletion.Results: The Syrian hamster is a suitable model for assessment of oncolytic adenovirus and vaccinia virus. Three low doses of adenovirus followed by three low doses of vaccinia virus resulted in a superior antitumor efficacy to the reverse combination, or six doses of either virus alone, against pancreatic and kidney tumors in Syrian hamsters. A total of 62.5% of animals bearing either tumor type treated with the sequential combination became tumor-free, accompanied by the induction of effective tumor-specific immunity. This enhanced efficacy was ablated by CD3+ T-cell depletion but was not associated with humoral immunity against the viruses.Conclusion: These findings show that sequential treatment of tumors with oncolytic adenovirus and vaccinia virus is a promising approach for cancer therapy and that T-cell responses play a critical role. Clin Cancer Res; 18(24); 6679–89. ©2012 AACR.