NEW YORK--Immunotherapy approaches have been used successfully to treat and even cure a very small subset of patients with advanced solid cancers. The challenge is to increase the types of cancer that are responsive to immunotherapy, Steven A. Rosenberg, MD, PhD, said at a symposium on cancer vaccines sponsored by the Cancer Research Institute.
Dr. Rosenberg and his colleagues at the NCI, where he is chief of surgery, have been using autologous tumor infiltrating lymphocytes (TILs)--lymphoid cells that can be cultured from tumors--plus high-dose interleukin-2 (IL-2) to treat patients with progressive malignancies, most notably melanoma. The patients had failed other treatments. A complete regression of all metastatic disease was achieved in 10% of patients.
By focusing on the ability of TILs to recognize melanoma antigens and identifying the antigens involved in the tumor recognition process, Dr. Rosenberg hopes to generate principles that can be applied to the treatment of other tumors.
He noted that TIL cells can be isolated that appear to be uniquely reactive against tumor-associated antigens from a variety of histologies--in about a fourth of patients with breast, colon, and ovarian cancers and non-Hodgkin's lymphomas.
Adoptive Transfer of MART-1
In a study reported this year, TILs were used to clone and sequence the genes that encode melanoma antigens, including MART-1 (melanoma antigen recognized by T cells). This gene encodes a previously undescribed transmembrane protein whose expression is restricted to melanoma, melanocyte cell lines, and human retina. Another gene identified encoded the glycoprotein gp100 and was recognized by the melanoma-specific antibody MB-45.
NCI researchers are using this information for the in vitro sensitization of cells directed against immunodominant peptides and for development of viral vaccines expressing these gene products. These in vitro sensitized anti-MART-1 cytotoxic T cells are 25- to 100-fold higher in lytic activity than conventional TILs, and secrete cytokines when co-cultured with the autologous target cells, he noted.