The aims of this investigation are to continue efforts to derive and to examine in vitro and in vivo the biological properties of long-term cultured, selected, and cloned tumor-specific T-cell lines. Experiments already completed give confidence that T-cell lines which bear tumor specificity can be raised against chemically induced murine sarcomas. These lines can be sustained for sufficiently long periods and in sufficiently high numbers for a wide range of biological studies and can be tested for the capacity to protect against tumor growth in vivo in potential immunotherapeutic models. To date over 50 antitumor cell lines have been derived and tested according to the protocols proposed originally. During this period, additional cloned T-cell lines have been isolated with tumor-specific partial protection. The thrust has been to rely more upon adoptive protection and DTH activity of the clones than upon in vitro cytotoxicity testing as previously used. It has proven difficult to extend active life beyond 50 days without loss of specific kill or clone death. The reasons for this are not understood; the lines which have been extended up to 200 days have all shown cytogenetic alteration, suggesting that they have spontaneously transformed. In vivo specific protective activity of the cloned lines observed during the first year of this grant has been confirmed. The data are now being prepared for publication. Briefly, if the specific cell lines are either mixed with the tumor before injection, if the tumor is in early ascites form and the cells are injected ip., or if the cells are injected directly into the tumor, protection is afforded. No protection can be demonstrated by cells administered by other routes. During the next period, intensive efforts will be focused upon providing preliminary experiments which appear to yield T-cell lines of helper phenotype, with tumor-specific activity demonstrated by D.T.H. (LB)
