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Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Cancer vaccines: moving beyond current paradigms
Jeffrey Schlom1, Philip M Arlen, James L Gulley
1Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. js141c@nih.gov
Abstract:
The field of cancer vaccines is currently in an active state of preclinical and clinical investigations. Although no therapeutic cancer vaccine has to date been approved by the Food and Drug Administration, several new paradigms are emerging from recent clinical findings both in the use of combination therapy approaches and, perhaps more importantly, in clinical trial design and end point analyses. This article will review recent clinical trials involving several different cancer vaccines from which data are emerging contrasting classic "tumor response" (Response Evaluation Criteria in Solid Tumors) criteria with "patient response" in the manifestation of increased patient survival post-vaccine therapy. Also described are several strategies in which cancer vaccines can be exploited in combination with other agents and therapeutic modalities that are quite unique when compared with "conventional" combination therapies. This is most likely due to the phenomena that (a) cancer vaccines initiate a dynamic immune process that can be exploited in subsequent therapies and (b) both radiation and certain chemotherapeutic agents have been shown to alter the phenotype of tumor cells as to render them more susceptible to T-cell--mediated killing. Consequently, evidence is emerging from several studies in which patient cohorts who first receive a cancer vaccine (as contrasted with control cohorts) benefit clinically from subsequent therapies.
Insights
Cancer vaccines are advancing, with new trials focusing on patient survival over tumor response. Combination therapies with vaccines show enhanced clinical benefits in patients receiving subsequent treatments.
Area of Science:
- Oncology
- Immunology
- Vaccinology
Background:
- The field of cancer vaccines is undergoing significant preclinical and clinical investigation.
- Despite no FDA-approved therapeutic cancer vaccines, emerging clinical data reveal new paradigms in combination therapy and trial design.
- Current research contrasts traditional tumor response criteria with patient survival outcomes post-vaccine therapy.
Purpose of the Study:
- To review recent clinical trials of various cancer vaccines.
- To analyze emerging data contrasting tumor response with patient survival.
- To describe novel combination strategies for cancer vaccines with other therapies.
Main Methods:
- Review of recent clinical trials involving diverse cancer vaccines.
- Analysis of data comparing Response Evaluation Criteria in Solid Tumors (RECIST) with patient survival metrics.
- Examination of unique combination therapy approaches exploiting vaccine-induced immune responses and chemo/radiotherapy effects.
Main Results:
- Emerging data suggest patient survival may be a more relevant endpoint than traditional tumor response for cancer vaccines.
- Cancer vaccines initiate dynamic immune processes that can be synergistically exploited by subsequent therapies.
- Radiation and chemotherapy can enhance tumor cell susceptibility to T-cell-mediated killing, particularly after vaccination.
Conclusions:
- Cancer vaccines are evolving, with a shift towards evaluating patient survival as a key endpoint.
- Novel combination strategies, leveraging vaccine-induced immunity and other modalities, offer unique therapeutic potential.
- Evidence indicates that initiating treatment with cancer vaccines can enhance clinical benefit from subsequent therapies.
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