Thursday, April 14, 2016

T cell compatible cancer chemotherapy synergizes with cancer adjuvant vaccine

Nowadays it is well acknowledged that optimal cancer treatment would require multi-pronged approach, for example, combining cancer chemotherapy with cancer antigen-specific vaccine to boost tumor-specific T cell response. However, such combination is not always feasible since (a) both tumor and activated T cells are highly proliferative cell types and (b) vast majority of chemotherapy drugs target cellular replication machinery. Basically, it is matter of trial and error to find T cell compatible chemotherapy drugs.


Most cervical cancers in humans are induced by human papillomavirus type 16 (HPV16). Initially, the authors showed that CarboTaxol synergized with HPV16-SLP vaccination in HPV16-positive TC-1 tumor-bearing mouse model.



Next, the authors noticed that CarboTaxol [and vaccine too] reduced level of CD11bhighGr1high myeloid [suppressor] population within tumor tissue.



Similar depletion of myeloid population was observed in blood samples of cervical cancer patients undergoing CarboTaxol therapy.


In fact, CarboTaxol treatment cycles significantly improved T cells proliferation in response to minor [bacterial recall antigen mixture, MRM)] and major HLA antigens [MLR].



Finally, combining CarboTaxol treatment with HPV16-SLP vaccination improved T cell stimulation in response to HPV16 antigens E6/E7.



In summary, this study indicates that CarboTaxol chemotherapy augments, rather than inhibits, tumor-specific T cell priming in response to HPV16-SLP vaccination.

David Usharauli


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