A model for CAN-3110 action as a function of HSV1 serology.
cancers, ’, inflammation, cancer, tumour
CANCERS, TUMOURS, INFLAMMATION, CANCER, TUMOUR, CYTOTOXICITY
In patients who are seropositive for HSV1, CAN-3110 elicits an initial augmented anti-HSV1 innate and T cell-mediated response (presumably by expansion and differentiation of memory into effector anti-HSV1 T cells) to clear the injected oHSV from tumours. This bystander T cell effect possibly mediates an effective antitumour effect by direct inflammation in the tumour and/or by stimulating ‘antigen spreading’ to also elicit T cell recognition of tumour antigens. In patients who are seronegative for HSV1, the absence of a rapid anti-HSV1 innate and T cell response leads to CAN-3110 replicative persistence with tumour growth overcoming viral-induced cytotoxicity and delayed immune activity against tumour antigens. The figure was generated using BioRender.com.In summary, single-timepoint intralesional injection of rHGG/rGBM with CAN-3110 enriches the tumour microenvironment with TILs, inducing defined changes in peripheral and tumour T cell repertoires and tumour transcriptomic signatures. These changes are particularly evident in patients who are seropositive for HSV1 and are associated with improved survival in this otherwise therapy-refractory cancer. These findings therefore provide human immunological and biological evidence supporting intralesional oncolytic modalities to convert the immunosuppressive TME characteristic of many solid cancers into a TME that is more favourable to immunologic rejection of the tumour. We are now set to determine whether multiple-timepoint injections lead to further improvements in this therapy (ClinicalTrials.gov: 