Adoptive immunotherapy using in vitro expanded lymphocytes (tumor infiltrating lymphocytes (TIL) or lymphokine activated killer cells (LAK)) can effectively treat tumor bearing animals and select patients with metastatic cancer. The recent identification and cloning of tumor associated antigens (TAA) now allows for the development of new therapeutic strategies. One such approach may be the adoptive transfer of peripheral blood lymphocytes (PEL), stimulated in vitro with peptides derived from TAA. The purpose of this study was to determine if the same T-cell clonotypes are expanded from TIL and PEL in individual patients. MART-1 reactive PEL and TIL cultures were generated from three patients by in vitro stimulation with an immunodorninant peptide of MART-1 (M9-27) and IL-2. All cultures had an HLA-A2 restricted, MART-1 specific CTL response. The TCR usage of these cultures was assessed by the DNA sequence analysis of TCR beta cDNA clones obtained by RACE. TCR analysis suggests a diverse TCR repertoire. In at least one patient, there appears the be predominant usage of V beta 2.1 by these MART reactive T-cells. However, these rearrangements were derived from multiple clonotypes since different V/D/J junctions were observed. The same clonotypes were found in both PBL and TIL from the same patient, suggesting peptide stimulated expansion in both biologic compartments. Therefore, it appears that T-cell clonotypes have the same potential for antigen driven expansion whether present in PBL or TIL.
|Publication status||Published - 1996|
ASJC Scopus subject areas
- Agricultural and Biological Sciences (miscellaneous)
- Biochemistry, Genetics and Molecular Biology(all)
- Cell Biology