Figure 2.

In vivo activity of LTX-401 on subcutaneous MCA205 fibrosarcoma in immunocompetent animals. Mouse fibrosarcoma MCA205 cells were injected subcutaneously in syngeneic C57BL/6 mice and palpable tumors arising thereof were treated with sequential intratumoral injections of 0.25 mg LTX-401 as indicated in (A). LTX-401 induced efficient oncolysis an effect that is reflected in reduced tumor growth (B), and increased overall survival (C) (Chi² test, **p < 0.01, n = 12). Rechallenge of animals cured from MCA205 fibrosarcoma (pooled from several experiments) with MCA205 several weeks after the initial therapy on the contralateral flank and challenged with syngeneic mouse AT3 breast cancer cells on the ipsilateral side resulted in efficient rejection of MCA205 but aggressive tumor growth of AT3 (D). Thus, LTX-401 caused the generation of immunological memory that sufficed in rejecting isogenic tumors. Similar effects were obtained when mouse lung cancer TC-1 cells were inoculated subcutaneously in syngeneic C57BL/6 mice and tumors and were treated when palpable with repeated injections of 0.25 mg LTX-401 intratumorally as shown in (A). LTX-401 induced efficient oncolysis and tumor control in some animals reflected in reduced tumor growth and cure of some animals (E), and increased overall survival (F) (Chi² test, ***p < 0.001). Some of the animals cured from subcutaneous TC-1 lung cancers were rechallenged with TC-1 several weeks after the initial therapy on the contralateral and challenged with syngeneic mouse MCA205 fibrosarcoma cells on the ipsilateral side. This maneuver resulted in efficient rejection of TC-1 but aggressive tumor growth of MCA205 (G). Thus, also in this model system LTX-401 caused the generation of immunological memory in cured animals that sufficed in rejecting isogenic tumors.