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Welcome to the Reisfeld Laboratory

The major objective of our research efforts is to develop novel and effective immunotherapies for cancer and to elucidate their mechanisms of action. We have progressed in these efforts thus far inducing potent cell-mediated host immune responses capable of eradicating disseminated metastases of melanoma, neuroblastoma and colon carcinoma in pathophysiologically relevant tumor models in syngeneic mice. These anti-tumor effects were achieved with recombinant antibody-cytokine fusion proteins effective in directing multifunctional cytokines into the tumor microenvironment, where they effectively activate and expand immune effectors, such as natural killer (NK) cells and T lymphocytes. Importantly, the CD8+ T cell-mediated eradication of disseminated metastases was found to be associated with a long-lived transferable systemic immunity that effectively protected mice against tumor challenges. The effective NK cell-mediated anti-tumor responses observed can be of considerable practical value in immune suppressed patients extensively pretreated with radio- and chemotherapies.

Effective tumor-protective immunity mediated by MHC class I-restricted CD8+ T cells was induced against a lethal challenge of colon carcinoma cells with a human CEA-based DNA vaccine carried by attenuated Salmonella typhimurium and administered by oral gavage to CEA-transgenic mice. Boosts with non-curative doses of a recombinant antibody-IL2 fusion protein further optimized this vaccine's efficacy, as it upregulated the expression of both co-stimulatory molecules B7.1, B7.2 and ICAM-1 on antigen-presenting cells and activity markers CD28, LFA-1, CD25 and CD69 on T cells. Effective T cell priming was evident by release of Th1 cytokines IFN-g, IL12 and GM-CSF. Taken together, results obtained thus far suggest that these novel immunotherapeutic approaches with recombinant antibody-cytokine fusion proteins and DNA vaccines may become useful for the treatment of malignancies in an adjuvant setting, particularly in patients with minimal residual disease.