Purging metastases in lymphoid organs using a combination of antigen-nonspecific adoptive T cell therapy, oncolytic virotherapy and immunotherapy.
In many common cancers, dissemination of secondary tumors via the lymph nodes poses the most significant threat to the affected individual. Metastatic cells often reach the lymph nodes by mimicking the molecular mechanisms used by hematopoietic cells to traffic to peripheral lymphoid organs. Therefore, we exploited naive T cell trafficking in order to chaperone an oncolytic virus to lymphoid organs harboring metastatic cells. Metastatic burden was initially reduced by viral oncolysis and was then eradicated, as tumor cell killing in the lymph node and spleen generated protective antitumor immunity. Lymph node purging of tumor cells was possible even in virus-immune mice. Adoptive transfer of normal T cells loaded with oncolytic virus into individuals with cancer would be technically easy to implement both to reduce the distribution of metastases and to vaccinate the affected individual in situ against micrometastatic disease. As such, this adoptive transfer could have a great therapeutic impact, in the adjuvant setting, on many different cancer types.
Molecular Medicine Program, Mayo Clinic, Rochester, Minnesota 55905, USA.
Jian
J
Qiao
Timothy
T
Kottke
Candice
C
Willmon
Feorillo
F
Galivo
Phonphimon
P
Wongthida
Rosa Maria
RM
Diaz
Jill
J
Thompson
Pamela
P
Ryno
Glen N
GN
Barber
John
J
Chester
Peter
P
Selby
Kevin
K
Harrington
Alan
A
Melcher
Richard G
RG
Vile
D000818:Animals; D000941:Antigens / Q000737:chemistry; D015179:Colorectal Neoplasms / Q000473:pathology; D007107:Immune System; D007167:Immunotherapy / Q000379:methods*; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008546:Melanoma, Experimental / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009369:Neoplasms / Q000473:pathology; D050504:Oncolytic Viruses / Q000378:metabolism*; D013154:Spleen / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D000941:Antigens