Despite numerous theoretical advantages cellular adoptive immunotherapy in malignant neoplasia has not resulted in a major therapeutic gain. The few exams of the successful adoptive immunotherapy of established tumors indicated that a number of prerequisites must be fulfilled in order that tumor inhibition be effected. The necessity for highly sensitized syngeneic cells in large numbers (100 million) presented major obstacles to the development of this therapeutic approach. The recent evolution of methodology which enables the in vitro propagation of sensitized T-cell lines which may be cloned for phenotypic determinants has provided a potentially compelling application to the cellular adoptive setting. Accordingly, the major objective of this endeavor is to develop a successful immunotherapy model utilizing an animal tumor system which has thus far been refractory to cellular transfer. This study will assess the efficacy of adoptively transferred in vivo sensitized IL-2 expanded T-cells in inhibiting the growth of micrometastases following the surgical removal of a primary tumor in a C3H adenocarcinoma model. The development of large numbers of clonally isolated IL-2 expanded phenotypically characterized T-cell populations would circumvent the significant disadvantages inherent in the use of heterogeneous populations. Efforts will be made to develop clonally derived lines with cytolytic and proliferative activity in an effort to analyze the mechanisms involved in successful adoptive transfer. In addition, the efficacy of in vivo administered IL-2, either alone or together with IL-2 expanded T-cells will be addressed as will the propriety of using cyclophosphamide together with adoptive transfer. Pilot experiments are proposed to address the intralesional use of IL-2. These investigations will serve as the preliminary phase of a program for the determination of the feasibility of this method of therapy in the clinical setting. Should these studies provide evidence to support the efficacy of cellular adoptive transfer a rational would become available for the formulation of clinical approaches in surgical adjuvant therapy.
