| Abstract: |
Purpose: Immunotherapy with vaccines, cytokines, and monoclonal antibodies against checkpoint molecules has been introduced into the clinical arena. Although all have demonstrated safety in clinical trials in patients with castrate metastatic prostate cancer, no one approach has been able to provide improved overall survival. This article is a review of the current issues and potential resolutions as to how we might go forward in developing and interpreting immunologic trials. Design: Phase I, II, and III trials showed that immunologic tolerance can be abrogated against specific tumor-associated antigens, but the immunologic readouts are suboptimal in determining whether a trial can go forward in its development. Results: Combinatorial approaches appear to be necessary for inducing immunogenicity and antitumor effects. Strategies include irradiated tumor cells lines, costimulatory molecules, or immune checkpoint inhibitors, which are in trials and are under intense scrutiny as to their impact on clinical end points such as time to disease progression and survival. Discussion: Strategies to enhance immunogenicity of vaccines and reassess how to effectively establish interpretable immunologic end points are under development and appear to be successful in affecting how these trials go forward. © 2008 by Lippincott Williams & Wilkins. |
| Keywords: |
survival; unclassified drug; prednisone; clinical trial; review; cancer growth; nonhuman; recurrent cancer; methodology; prostate specific antigen; gene; bcg vaccine; cancer immunotherapy; metastasis; ovary cancer; carcinoembryonic antigen; antineoplastic activity; drug effect; gene vector; genetic transduction; genetic vectors; transduction, genetic; cancer resistance; docetaxel; monoclonal antibody; cancer hormone therapy; fever; prostate cancer; prostate-specific antigen; prostatic neoplasms; cytokine; immunology; cytokines; antibodies, monoclonal; rigor; cellular immunity; immunotherapy; cancer vaccine; cancer vaccines; immunogenicity; prostate tumor; montanide isa 51; antigens, cd; provenge; cytotoxic t lymphocyte antigen 4; granulocyte macrophage colony stimulating factor vaccine; drug treatment failure; humoral immunity; leukocyte antigen; lymphocyte function associated antigen 3; adoptive immunotherapy; recombinant granulocyte macrophage colony stimulating factor; genes, cdc; vaccines; b7 antigen; cd86 antigen; recombinant interleukin 2; antigens, differentiation; cell strain lncap; differentiation antigen; virus vector; mucins; qs 21; cytotoxic t-lymphocyte antigen 4; checkpoint molecule; fowlpox; cytotoxic t lymphocyte antigen-4; gvax; prostate-specific membrane antigen; sipuleucel-t; acid phosphatase prostate isoenzyme; intracellular adhesion molecule 1; pa 2024; tg 4010
|
