SHORT-TERM EX-VIVO ACTIVATION OF SPLENOCYTES WITH ANTI-CD3 PLUS IL-2 AND INFUSION POST-BMT INTO MICE RESULTS IN IN-VIVO EXPANSION OF EFFECTOR-CELLS WITH POTENT ANTI-LYMPHOMA ACTIVITY

We investigated the proliferation and therapeutic utility of anti-CD3 activated splenocytes infused into mice following BMT. Using congenic mouse strains we demonstrated that splenocytes activated briefly ex vi vo with anti-CD3 plus IL-2 (T-activated killer cells or T-AK) and infu sed intravenously following BMT had a greater expansion in blood, sple en and BM compared with splenocytes stimulated with IL-2 alone. T-AK c ells recovered from blood, spleen and BM consisted predominantly of CD 8(+) T cells. A single infusion of T-AK cells given on day +1 post-syn geneic BMT and sustained in vivo with liposomal encapsulated IL-2, sig nificantly increased survival of mice with BDL-2 lymphoma when compare d with mice receiving saline and those treated with IL-2 liposomes alo ne. The anti-tumor effect of T-AK cells was significantly enhanced whe n IL-2 was given by continuous infusion compared with bolus injections . Depletion studies confirmed that the CD8(+) T-AK cells were mainly r esponsible for the anti-tumor effect against BDL-2 lymphoma. Our findi ngs demonstrate that brief ex vivo activation of splenocytes with anti -CD3 plus IL-2 results in in vivo proliferation of effector cells with potent anti-tumor activity following BMT.