Abstract
Adoptive T cell therapy has emerged as a promising treatment for cancer. However, it is unknown whether adoptively transferred anti-tumor T cells can form immunological memory and provide continuous protection against cancer metastasis. Herein, we used TCR transgenic Pmel-1 CD8+ T cells as a model to investigate whether early transferred Pmel-1 CD8+ T cells can generate immunological memory to prevent later melanoma metastasis. Upon stimulation with the cognate melanoma-associated hgp100 antigen, in vitro cultured Pmel-1 CD8+ T cells developed into effector T (Teff) cells that exhibited potent cytotoxic activity against B16F10 melanoma cells. Next, B16F10 melanoma cells were intravenously injected into C57BL/6 (B6) mice to establish experimental lung metastasis. In vitro generated Pmel-1 Teff cells were adoptively transferred into the mice on the same day of or three weeks prior to B16F10 cell inoculation. We found that adoptive Pmel-1 Teff cell therapy significantly inhibited the B16F10 lung metastasis and prolonged the animal survival. Importantly, Pmel-1 Teff cells transferred three weeks prior to tumor inoculation were as potent as the Pmel-1 Teff cells transferred on the same day in inhibiting melanoma metastasis. Hence, our results suggest that adoptive CD8+ Teff cell therapy generates immunological memory that continuously protect against melanoma metastasis.
Original language | English (US) |
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Pages (from-to) | 7262-7274 |
Number of pages | 13 |
Journal | American Journal of Translational Research |
Volume | 12 |
Issue number | 11 |
State | Published - 2020 |
Keywords
- Adoptive cell therapy
- B16 melanoma
- CD8 T cell
- Cancer metastasis
- IVIS
- Pmel-1
ASJC Scopus subject areas
- Molecular Medicine
- Clinical Biochemistry
- Cancer Research