Our laboratory's major work is the development and evaluation of immunologic reagents in patients with malignancy. Preparation of single cell suspension from human tumors and derivation of cloned and bulk populations of autologous lymphocytes reacting to them remain a major goal. In the last year, over 100 tumor preparations have been evaluated and currently attempts to grow tumor reactive cells directly from tumors is being evaluated. We have been able to clone lymphoid cells directly from human tumors (TILs) with reactivity unique to autologous melanoma. In addition we are evaluating new technologies for the early separation and growth of TILs. We have evaluated the susceptibility of tumor cells to lysis by TILs as well as cells with NK and lymphokine activated killer (LAK) activity. We have demonstrated that 100-1000 fold increase in tumor susceptibility to lysis by some of these reagents may occur with preincubation of the targets with gamma interferon (delta-IFN) and tumor necrosis factor (TNF), two recently cloned recombinant human cytokines. We have investigated the in vivo use of Interleukin-2 (IL-2) in patients and reported in detail the responses seen in patients receiving IL-2 IV or IP. Both partial and complete responses have been noted in patients with renal cell tumors as well as melanoma. Future effects include therapeutic application of cloned TILs and development of protocols for pretreatment of the host with TNF and delta-IFN on immunotherapy protocols. Investigation of the use of monoclonal antibodies in conjunction with IL-2 or adoptive therapy with IL-2 activated cells has been carried out in our laboratory. We have evaluated heteroconjugated antibodies as well as antibodies to melanoma given alone as diagnostic agents or in conjunction with IL-2. Future efforts include a protocol designed to administer IL-2 at high doses in conjunction with therapeutic doses of monoclonal antibodies to patients with colorectal tumors as well as melanoma.
