Associate Investigator Pathology, Mass General Research Institute

antigens, neoplasm; immunotherapy; lymphocytes, tumor-infiltrating; mart-1 antigen; melanoma; t-lymphocytes; tumor escape

Dr. Kurnick's activities in cellular immunology are focused on the ability of in vivo activated T lymphocytes to recognize antigens expressed on autologous human tumors. Recent work in human melanomas has indicated that tumor cells can reversibly down-modulate expression of tumor-associated antigens, allowing them to escape immune recognition and destruction.

Using cellular and molecular technologies, Dr. Kurnick and his associates have shown that gene regulatory events allow tumors to escape and that certain activations pathways and transcription factors can be used to reestablish antigen expression in tumors that can no longer be recognized.

Using technologies including T lymphocyte and tumor cell cloning, together with molecular techniques to evaluate gene expression and biochemical analysis of activation pathways, the laboratory utilizes a variety of in vitro technologies to develop novel means for enhancing the immune response to tumors.

The laboratory has discovered several pathways to enhance antigen expression in melanomas and gliomas, including MAP-Kinase inhibitors and Interferon-beta. Using a lentiviral transduction protocol, the laboratory has inserted melanoma-specific T cell receptors into normal blood lymphocytes and T cell tumors and has developed a cellular assay for screening large libraries of compounds to discover new agents and mechanisms for controlling tumor cell differentiation and T cell targeting of tumor cells. The transduced T cell receptors can be used clinically to target tumor cells with autologous lymphocytes.