Vienna Conference Looks Promising, page-6

Here is another abstract being presented by VLA at the European Cancer Conference (comes up in search of "A21" as per my previous post).  This abstract also seems to be very positive:-

Phase II CALM extension study: Enhanced immune-cell infiltration within the tumour micro-environment of patients with advanced melanoma following intralesional delivery of Coxsackievirus A21
R.H.I. Andtbacka, B. Curti, S. Hallmeyer, Z. Feng, C. Paustian, C. Bifulco, B. Fox, M. Grose, B. Davies, R. Karpathy, D. Shafren
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Background: CAVATAK, an oncolytic immunotherapy, is abio-selected oncolytic strain of Coxsackievirus A21 (CVA21). Followingintratumoral (IT) injection, CVA21 preferentially infects ICAM-1 expressingtumour cells, resulting in viral replication, cell lysis, and a systemicanti-tumour immune response. The Phase II CALMstudy investigated the efficacy and safety of IT CVA21 in patients (pts) withadvanced melanoma. The primary endpoint was achieved with 22 of 57 (38.6%) evaluable ptswith durable responses observed inboth injected and uninjected melanoma metastases, suggesting the generation ofsignificant host anti-tumour responses. Pre-clinical studies in animmune-competent mouse melanoma model revealed that combinations of IT CVA21and anti-PD-1 or anti-CTLA-4 mAbs mediated significantly greater antitumoractivity compared to either agent alone. Here we report on a continuation studyaimed at understanding the immune-mediated effects of CVA21 in melanoma pts.
Methods: To further elucidate the nature of the systemicanti-tumor responses, a CALM study extension (NCT01227551)cohort of 13 pts received up to 3 x 10⁸ TCID₅₀ CVA21 ITon study days 1,3,5, 8, 22, and then q3wks for a further 6 injections.Sequential tumour biopsies of both injected and uninjected lesions were monitoredfor levels of viral replication and evidence of viral-induced immune activationwithin the tumour micro-environment using multi-spectral imaging and NanoStringdigital RNA counting.
Results: Activetumour-specific cytolytic viral replication is postulated to contribute to thegeneration of systemic anti-tumor responses. CVA21 replication within thetumour micro-environment resulted in increases in tumour-infiltratinglymphocytes (TILs), especially CD8⁺ cells and increased expressionof PD-L1⁺ cells as assessed by. Analysis of pre- and post-treatmentbiopsies showed sizable up-regulation of a number of immune modulationelements, including Interferon-induced 17 kDa protein, Interferon-inducedGTP-binding protein Mx1, Granulysin, Granzyme B, Perforin, CXCL10 and CXCL11.In 2 patients who had previously progressed on treatment with anti-CTLA-4 mAband anti-PD-1 mAb, tumour biopsies prior to CVA21 treatment indicated very few TILs.After 3 injections with CVA21, there was a robust increase in TILs, especiallyCD8⁺ cells with an associated concomitant increase in PD-L1⁺cells.
Conclusions: Intralesional administration of CVA21 can notably influence the dynamics of the tumour micro-environment as evidenced byincreases in immune cell infiltrates and immune-related response genes. As such, the oncolytic andimmunotherapeutic activities of CVA21 warrant further clinical evaluation incombination with immune checkpoint inhibitor strategies (anti-CTLA-4, anti-PD-1or anti-PD-L1).
No conflict of interest.