Collaboration of chimeric antigen receptor (CAR)-expressing T cells and host T cells for optimal elimination of established ovarian tumors

Paul Spear, Amorette Barber, Charles L Sentman
Oncoimmunology 2013 April 1, 2 (4): e23564
23734311
Conditioning strategies that deplete host lymphocytes have been shown to enhance clinical responses to some adoptive T-cell therapies. However, host T cells are capable of eliminating tumor cells upon the relief of immunosuppression, indicating that lymphodepletion prior to T-cell transfer may reduce optimal tumor protection elicited by cell treatments that are capable of shaping host immunity. In this study, we show that adoptively transferred T cells bearing a chimeric antigen receptor (CAR) harness endogenous T cells for optimal tumor elimination and the development of a tumor-specific memory T cell response. Mice bearing ID8 ovarian cancer cells were treated with T cells transduced with a NKG2D-based CAR. CAR-expressing T cells increased the number of host CD4(+) and CD8(+) T cells at the tumor site in a CXCR3-dependent manner and increased the number of antigen-specific host CD4(+) T cells in the tumor and draining lymph nodes. In addition, the administration of CAR-expressing T cells increased antigen presentation to CD4(+) T cells, and this increase was dependent on interferon γ and granulocyte-macrophage colony-stimulating factor produced by the former. Host CD4(+) T cells were sufficient for optimal tumor protection mediated by NKG2D CAR-expressing T cells, but they were not necessary if CD4(+) T cells were adoptively co-transferred. However, host CD4(+) T cells were essential for the development of an antigen-specific memory T-cell response to tumor cells. Moreover, optimal tumor elimination as orchestrated by NKG2D CAR-expressing T cells was dependent on host CD8(+) T cells. These results demonstrate that adoptively transferred T cells recruit and activate endogenous T-cell immunity to enhance the elimination of tumor cells and the development of tumor-specific memory responses.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read
23734311
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"