Immunologic and therapeutic evaluation of a synthetic peptide vaccine for the treatment of patients with metastatic melanoma

S A Rosenberg, J C Yang, D J Schwartzentruber, P Hwu, F M Marincola, S L Topalian, N P Restifo, M E Dudley, S L Schwarz, P J Spiess, J R Wunderlich, M R Parkhurst, Y Kawakami, C A Seipp, J H Einhorn, D E White, S A Rosenberg, J C Yang, D J Schwartzentruber, P Hwu, F M Marincola, S L Topalian, N P Restifo, M E Dudley, S L Schwarz, P J Spiess, J R Wunderlich, M R Parkhurst, Y Kawakami, C A Seipp, J H Einhorn, D E White

Abstract

The cloning of the genes encoding cancer antigens has opened new possibilities for the treatment of patients with cancer. In this study, immunodominant peptides from the gp100 melanoma-associated antigen were identified, and a synthetic peptide, designed to increase binding to HLA-A2 molecules, was used as a cancer vaccine to treat patients with metastatic melanoma. On the basis of immunologic assays, 91% of patients could be successfully immunized with this synthetic peptide, and 13 of 31 patients (42%) receiving the peptide vaccine plus IL-2 had objective cancer responses, and four additional patients had mixed or minor responses. Synthetic peptide vaccines based on the genes encoding cancer antigens hold promise for the development of novel cancer immunotherapies.

Figures

Fig. 1
Fig. 1
Cancer regression in patients receiving immunization with 209-2M peptide in IFA plus IL-2. top left, Regression of multiple lung metastases in a 47-year-old female (patient I in Table 5). bottom left, Regression of two brain metastases in a 42-year-old female (patient k). This patient had four brain metastases all of which underwent significant regression, above, Regression of multiple cutaneous and subcutaneous metastases in a 44-year-old male (patient c). Significant regression was seen by 8 days after starting treatment.

Source: PubMed

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