ISPO

Association of clinical and immunological responses to an autologous, hapten-modified human cancer vaccine.

D. Berd, MD

Thomas Jefferson University, Philadelphia, PA, USA.

Aim - We have devised a novel approach to active immunotherapy based on modification of autologous cancer cells with the hapten, dinitrophenyl (DNP). The treatment program consists of low dose cyclophosphamide followed by multiple intradermal injections of DNP modified autologous tumor cells mixed with BCG. Here we present the clinical results of vaccine treatment and analyze the correlation with immunological responses. Methods - We have tested the vaccine in two types of clinical trials: 1)stage IV melanoma patients with measurable metastases, and 2)melanoma patients with bulky, resectable stage III disease. Results - The stage IV trial included 83 patients evaluable with surgically incurable metastatic melanoma. There were 11 anti-tumor responses: 2 complete, 4 partial, and 5 mixed. Both complete responses and two of the four partial responses occurred in patients with lung metastases. Response durations were as follows: partial responses 5,6,8, and 47+ months; complete responses 12, 29 months. Tumor regression required at least 4 months to become evident, and in two cases maximum regression was not observed until one year after beginning treatment. Delayed-type hypersensitivity (DTH) to DNP-modified and unmodified autologous melanoma cells was induced in 87% and 42% of patients, respectively. The DTH response to unmodified cells was significantly associated with prolonged survival. The stage III trials included 214 melanoma patients who had been rendered disease-free by resection of palpable, large (³3 cm) regional lymph node metastases. With a median follow-up time of 5.1 years (2.5-10.9 years) the 5?year overall survival (OS) rate is 46% (one nodal site=48%, in transit metastases=50%, two nodal sites=36%). Again, the induction of DTH to unmodified autologous tumor cells was associated with significantly longer survival, which was confirmed in a multivariate analysis. Conclusions - This vaccine approach appears to induce clinical responses that are dependent on the development of a T cell-mediated response to as yet unidentified melanoma antigens.

KEY WORDS: Melanoma, Immunotherapy.

For more information, contact d_berd@mail.jci.tju.edu

Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Immunotherapy.

http://www.cancerprev.org/Journal/Issues/26/101/1295/4694