Figure 4.

Combination of single LTX-401 treatment with immune checkpoint blockade increases its efficacy. C57BL/6 mice subcutaneously implanted with MCA205 fibrosarcoma were injected intratumorally when tumors became palpable with a single injection of 0.25 mg LTX-401 as indicated in (A). Immune checkpoint blockade was mounted by sequential injections of monoclonal antibodies targeting CTLA-4 or PD-1 alone or in combination at day 6, 9 and 12 post treatment. LTX-401 induced efficient oncolysis which is reflected in reduced tumor growth and tumor clearance in some animals. This effect was increased in combination with CTLA-4 and PD-1 cotreatment as depicted in separate tumor growth curves (B-E) and overall survival plots (Chi² test, **p < 0.01) (F-H). Rechallenge of animals cured from MCA205 fibrosarcoma with MCA205 several weeks after the initial therapy on the contralateral and challenged with syngeneic mouse TC-1 lung cancer cells on the ipsilateral side resulted in efficient rejection of MCA205 but aggressive tumor growth of TC-1 (I). Thus, LTX-401 caused the generation of immunological memory that led to the rejection of isogenic tumors.