CLONAL T-CELL EXPANSION INDUCED BY INTERLEUKIN-2 THERAPY IN BLOOD ANDTUMORS

In a phase I clinical trial on the effects of preoperative adjuvant IL -2 therapy given to patients undergoing hepatic resection of colorecta l adenocarcinoma metastases, we monitored the putative induction of T cell clonal expansion in both tissues and blood, The presence of T cel l clonotypes was analyzed with a PCR-based method that determines V-D- J junction size patterns in T cell receptor (TCR) V beta subfamilies i n samples before and after a 5-d IL-2 infusion, This high resolution m ethod analyzing CDR3 sizes of TCR transcripts was used in conjunction with FACS(R) analysis of the corresponding T cell subpopulations with TCR V beta-specific mAb. At time of surgery (day 8 after starting IL-2 ), we found in the three patients analyzed with V beta-C beta primers multiple dominant T cell clonotypes in the tumor and peritumoral tissu es which had probably expanded as a result of therapy, In three contro l patients not treated with IL-2, multiple oligoclonal patterns were n ot observed with this set of primers, In the fourth control patient a unique V beta 21-C beta CDR3 pattern which corresponds to two dominant clonotypes was found in the tumor. The same dominant clonotypes ident ified in the tumor after IL-2 were also detectable in the blood and co mparison of the profiles obtained before and after IL-2 therapy indica tes that they were induced by IL-2. The relative expansion of the corr esponding T cell subpopulations was maintained for varying periods of time after surgery (4-7 d and almost 2 yr in one case). Together, thes e results indicate that IL-2 induces marked expansion of several T cel l clones. Systemic IL-2 administration may represent, either alone or as a vaccine adjuvant, an appropriate way of boosting antigen-specific immune responses.