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Murine rhabdomyosarcoma is immunogenic and responsive to T‐cell‐based immunotherapy
Author(s) -
Meadors Joanna L.,
Cui Yonghzi,
Chen QingRong,
Song Young K.,
Khan Javed,
Merlino Glenn,
Tsokos Maria,
Orentas Rimas J.,
Mackall Crystal L.
Publication year - 2011
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.23048
Subject(s) - medicine , immunotherapy , rhabdomyosarcoma , immunogenicity , immune system , cancer research , foxp3 , t cell , immunology , melanoma , adoptive cell transfer , oncolytic virus , pathology , sarcoma
Background Immunotherapies targeting cellular immunity are currently approved for treatment of melanoma, renal cell carcinoma, and prostate cancer. Studies on the immunogenicity and immune responsiveness of pediatric tumors are limited, therefore, it remains unclear to what extent T‐cell‐based immunotherapy holds promise for pediatric solid tumors. Procedure A new rhabdomyosarcoma cell line (M3‐9‐M) was derived from an embryonal rhabdomyosarcoma (ERMS) occurring in a C57BL/6 mouse transgenic for hepatocyte growth factor and heterozygous for mutated p53. Primary tumors and metastases derived from M3‐9‐M were studied for similarities to human ERMS, and for immunogenicity and immune responsiveness. Results Primary and metastatic tumors develop after orthotopic injection of M3‐9‐M into immunocompetent C57BL/6 mice, which mirror human ERMS with regard to histology, gene expression, and metastatic behavior. Whole cell vaccination using irradiated M3‐9‐M cells or M3‐9‐M‐pulsed dendritic cells (DC)‐induced tumor‐specific T‐cell responses that prevent tumor growth following low‐dose tumor injection, and slow tumor growth following higher doses. Administration of anti‐CD25 moAbs to deplete CD4 + CD25 + FOXP3 + regulatory T cells prior to tumor vaccination enhanced the potency of the ERMS tumor vaccine. Adoptive immunotherapy with M3‐9‐M primed T cells plus DC‐based vaccination resulted in complete eradication of day 10 M3‐9‐M derived tumors. Conclusions M3‐9‐M derived murine ERMS is immunogenic and immunoresponsive; regulatory T cells contribute to immune evasion by murine rhabdomyosarcoma. Adoptive immunotherapy with DC vaccination can eradicate low tumor burdens. Future work will seek to identify the tumor‐associated antigens that mediate protective and therapeutic immunity in this model. Pediatr Blood Cancer 2011; 57: 921–929. © 2011 Wiley‐Liss, Inc.