EVIDENCE FOR OLIGOCLONAL T-CELL RESPONSE IN A METASTASIS OF RENAL-CELL CARCINOMA RESPONDING TO VACCINATION WITH AUTOLOGOUS TUMOR-CELLS AND TRANSFER OF IN-VITRO-SENSITIZED VACCINE-DRAINING LYMPH-NODE LYMPHOCYTES

Peripheral blood lymphocytes (PBL) and tumor-infiltrating lymphocytes (TIL) of a patient with von Hippel-Lindau disease and renal cell carci noma were studied for the T-cell receptor beta chain variable region ( TCR-Vbeta) repertoire. The patient was vaccinated with irradiated auto logous tumor cells from a renal tumor mass, a vaccine-draining lymph n ode was removed, and lymphocytes were cultured in the presence of auto logous tumor cells and low-dose interleukin 2 (IL2). These lymphocytes were adoptively transferred to the patient together with systemic IL2 (30,000 IU/kg every 8 h). Analysis of TCR-Vbeta expression was perfor med by polymerase chain reaction in PBL before, during, and after ther apy, in vaccine-draining lymph node lymphocytes, and in TIL obtained f rom moderately infiltrated, nonresponding renal tumor mass and from a more intensely infiltrated lung metastasis, which was responding to tr eatment. Significant differences in the expression of TCR-Vbeta13.1 by T-cells recovered from these various sites were observed. Also, TIL r ecovered from the responding lung metastasis and cultured in the prese nce of IL2 gave rise to autologous tumor-reactive CD4+ T-cells, wherea s the nonresponsive renal tumor yielded a mixture of T- and natural ki ller cells. In PBL obtained prior to treatment and during IL2 therapy, expression of Vbeta13.1 was 0.7 and 1.8%, respectively, of the total Vbeta gene repertoire. Fresh vaccine-draining lymph node lymphocytes c ontained 5.9% of Vbeta13.1-expressing T-cells. After IL2 therapy, Vbet a13.1 gene expression increased to 5.4% in PBL. In the nonresponding t umor mass, the frequency of Vbeta13.1 gene expression among TIL was 12 %, whereas in the responding, highly infiltrated nodule, it was 28%, w ith a striking loss of expression of other Vbeta gene families. Sequen cing of the amplified product of Vbeta13.1 complementary DNA from the responding pulmonary metastasis showed restrictions in the complementa rity-determining region 3. Thus, in vivo expansion of Vbeta13.1-expres sing CD4+ T-cells, possibly in response to a tumor-associated antigen, occurred in the responding tumor mass following this form of therapy and correlated with tumor course.