Results of a Phase I/II Randomized Immunotherapy Trial Testing Adoptive Transfer of Co-Stimulated Autologous T Cells and Pneumococcal Conjugate Vaccine (PCV) Immunization after Autotransplantation for Myeloma (MM).

Although immunizations against microbial infections are recommended following autologous stem cell transplantation (ASCT), the antibody responses are often suboptimal. To assess improved immunization strategies, we tested the ability of autologous T cells that were co-stimulated ex vivo with anti-CD3 and -CD28 coated beads as part of their therapy for MM, as well as pre-ASCT immunization to enhance the antibody response to PCV post-ASCT. Subjects were randomized to receive PCV (groups 1 and 2) or no immunization (groups 3 and 4) before T cell harvest, and subsequent mobilization chemotherapy. All subjects received PCV at days 30 and 90 post-ASCT; however, groups 1 and 3 were given T cells before (day 12) post-ASCT PCV immunization, while groups 2 and 4 received T cells after PCV immunization (day 100). Patients receiving adoptive T cell therapy for MM without PCV immunization (group 5) served as controls. The results of the adoptive transfer of T cells on MM therapy are reported elsewhere. Anti-pneumococcal (Pn) antibody levels for serotypes 6B, 14, 23F, 19F were measured in sequential samples for up to 180 days for each patient by ELISA (response defined as ≥ 2-fold increase over baseline and ≥ 0.5 μg/ml) and opsonophagocytosis assay (OPA) (response defined as ≥ 1-log bacterial kill or ≥ 70% kill when ≤ 30% kill at baseline).

Responses in group 1 were of longer duration and greater magnitude than in other groups. We conclude that (1) MM patients immunized with PCV pre-ASCT respond better to PCV post-ASCT; (2) T cell administration before PCV immunization enhances protective anti-Pn antibody levels and for a longer duration. Our vaccine schedule that leads to improved PCV responses may also be used to improve the responses of ASCT patients to other microbial and perhaps cancer vaccines. (This study was supported by NIH contract N01-AI-85342 and LSA SCOR #7000-002).