What is therapeutic tumor vaccination?

Updated: Mar 20, 2018
  • Author: Crystal L Mackall, MD; Chief Editor: Jennifer Reikes Willert, MD  more...
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Answer

The efficacy of graft-versus-leukemia in eradicating leukemia illustrates the potential of T cells as effectors of antitumor activity in allogeneic settings. To exploit T-cell reactivity to autologous malignancies, existent weak tumor–directed immune responses must be amplified to result in meaningful antitumor effects. This is particularly challenging for cancer because tumor antigens frequently represent overexpressed self-antigen, for which the quality and quantity of antigen-reactive T cells is limiting.

Therapeutic tumor vaccination is a strategy that initiates a dynamic process of activating the host’s own immune system against a tumor antigen. The immunologic tolerance induced by tumor antigens during the course of primary tumor growth is not absolute and can be overcome through specific immunization with professional APCs or by transducing tumor cells with cytokine or costimulatory receptor-encoding genes. [66]

Although tumor vaccines alone do not induce clinically meaningful antitumor effects in patients with measurable tumor burdens, the usefulness of such immune-based therapies is likely to be optimal in patients with minimal residual disease. [67, 68]

Randomized studies comparing outcomes following tumor vaccination for patients with a high risk of disease recurrence have only rarely been conducted.

Of the 9 vaccines tested in phase III trials thus far, only 1 showed a reduction (31%) in the hazard rate for progression in asymptomatic, metastatic, hormone-refractory prostate cancer: sipuleucel-T (Provenge), which is composed of autologous APCs that express prostatic acid phosphatase and granulocyte-macrophage colony-stimulating factor (GM-CSF). [69] The trial was not designed to look at overall survival as a primary endpoint, but the group who received sipuleucel-T had a 4.5-month increase in overall survival. [69]


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