Murine Factor X Matched Antibody Pair

In an attempt to find a new class of cytotoxic agents, a series of 3,6-disubstituted-[1,2,4] triazolo[3,4-b] [1,3,4]thiadiazoles have been synthesized using undecenoic acid and various cinnamic acids. The structures of the synthesized compounds have been confirmed using H-1 and C-13 NMR, IR and mass spectroscopy. The prepared compounds have been evaluated for their in vitro cytotoxic activities against four human cancer cell lines namely, HeLa, B16-F10, SKOV3, MCF7 and CHO-Kl Normal Cell line using MTT assay. Compounds 6a and 6h show promising activity against HeLa (IC50 value 8.92 M) and SKOV3 cell lines (IC50 value 9.43 AM). Majority of the compounds show significant activities against HeLa cell line with the IC50 values ranging from 8.92 to 13.44 M. All the compounds show good activity against SKOV3 cell line with the IC50 values ranging from 9.43 to 19.34 M. Majority of the compounds are non toxic towards the Chinese hamster ovary (CHO-KI) normal cell line.

Immunotherapy has changed the oncology landscape during the last decade and become standard of care for several cancers. The combinations of immunotherapy with other treatment modalities are also being investigated. One of the challenges to investigate such combinations is to identify suitable mouse models for the pre-clinical experiments. In the past, we and other researchers showed that murine B16-F10 melanoma in C57Bl6 mice is refractory to treatment with immune checkpoint inhibitors. In this work we studied the suitability of an alternative syngeneic model, Cloudman S91 murine melanoma in DBA/2 mouse (DBA/2NCrl), to study the combination of immunotherapy targeting PD-1 and radioimmunotherapy targeting melanin. DBA/2 male and female mice were injected subcutaneously with 3-6 million Cloudman S91 cells. When the tumors reached similar to 150 mm(3) volume, the animals were treated intraperitoneally with PBS (sham), h8C3 unlabeled (cold) antibody to melanin, immunotherapy with anti-PD-1 antibody, radioimmunotherapy with 213Bismuth (213Bi)-labeled h8C3 antibody, or several combinations of immunotherapy and radioimmunotherapy. Treatments with immunotherapy alone produced very modest effect on the tumor size, while combination therapy resulted in significant slowing down of the tumor growth, increased animal survival, and no decrease in animal body weight. We conclude that Cloudman S91 murine melanoma in DBA/2 mouse is a suitable model to evaluate combination of immunotherapy of melanoma with tangentially targeted treatments.