In vitro induction of immune responses to shared tumor-associated antigens in rhabdomyosarcoma.

PURPOSE: Currently, novel therapies to improve survival of patients with rhabdomyosarcoma (RMS) are being investigated. One of the new approaches involves immunotherapy using tumor-specific T-lymphocytes. An effective prolonged immune-mediated response against tumor cells is dependent upon the response of helper T-lymphocytes (HTLs) to tumor-associated antigens in the presence of histocompatibility lymphocyte antigen surface proteins.

METHODS

Rhabdomyosarcoma tumor lysate-pulsed human dendritic cells were used to stimulate HTL precursors (naive CD4+ T-cells) in vitro. After 3 rounds of antigen stimulation with antigen-presenting cells, the T-cells were tested for reactivity (T-cell proliferation assays) against a large panel of tumor lysate-pulsed autologous antigen-presenting cells.

RESULTS

Using peripheral blood mononuclear cells from normal naive donors, we have been able to generate HTL clones that recognize and proliferate to multiple tumor cell lines. The HTLs were induced using lysate from a single alveolar RMS tumor cell line (RMS13). The clones generated recognized all of the alveolar RMS cell lines (RMS13, Rh18, Rh28, Rh30, and Rh41), prostate cancer cell lines (LNCAP and LAPC4), melanoma cell lines (Mel 624 and G361), and breast cancer cell line (SKBR3). Helper T-lymphocytes recognition was also confirmed by interferon-gamma production. The clones did not recognize colon, lymphoma, ovarian carcinoma, ERMS or Epstein-Barr virus (EBV) transformed B-cells. This recognition was histocompatibility lymphocyte antigen class II restricted and was not an allogeneic response.

CONCLUSION

The results of this work demonstrate that HTLs, exposed to RMS lysate, are able to recognize and respond to a broad range of tumor types suggesting that a common antigen exist among these different tumors. These findings suggest novel treatment strategies for patients with RMS using tumor lysate to induce antitumor immune responses.