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.
Such combination was recently described in new paper published in Science Translational Medicine. Here, the authors showed that cervical cancer treatment with CarboTaxol (carboplatin + paclitaxel) synergizes with therapeutic T cell vaccine that consisted of HPV16 overlapping synthetic long peptides (HPV16-SLPs) admixed with adjuvant Montanide ISA-51.
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
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
