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
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.