Combinations of irs/stat3 dual modulators and anti pd-1/pd-l1 antibodies for treating cancer
A PD-L1, PD-1 technology, applied in the direction of antibodies, drug combinations, antibody medical components, etc., can solve problems such as unmet needs
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[0184] During the preparation of the pharmaceutical compositions according to the invention, the active ingredient is usually mixed with a carrier or excipient, which may be solid, semi-solid or liquid material. Said compositions can be taken as tablets, pills, capsules, pellets, granules, powders, lozenges, sachets, cachets, elixirs, suspensions, dispersions, emulsions, solutions, syrups, aerosols (as solid or in a liquid medium), ointments containing, for example, up to 10% by weight of the active compound, soft and hard gelatin capsules, suppositories, sterile injectable solutions and sterile packaged powders. Each possibility represents a separate embodiment of the invention.
[0185] The carrier may be any conventionally used carrier and is limited only by chemical-physical considerations such as solubility and lack of reactivity with the compounds of the invention and route of administration. The choice of carrier will be dictated by the particular method used to admini...
Embodiment 1
[0208] Example 1: Compound 4 and pembrolizumab Combinatorial combination turns non-responsive tumors into responsive tumors and blocks tumor progression
[0209] Experimental system :
[0210] Patient-derived xenografts (PDX) of esophagogastric junction adenocarcinoma biopsies were implanted subcutaneously (SC) into NodScid mice. On the first day of treatment, peripheral blood mononuclear cells (PBMC) from the same patient were injected intravenously into the mice (double autologous).
[0211] ■ Fresh human primary esophagogastric junction adenocarcinoma biopsies were implanted subcutaneously (SC) into NSG mice (P0).
[0212] Subcutaneous Implantation of Human Primary Tumor Biopsy Samples in NodScid Mice
[0213] Tumors (P3) were extracted from mice, measured, cut into 1-2mm pieces and transferred to gentleMACS tubes containing sterile saline. Tumor volume adjusted to 1.5 mm with saline 3 Tumor volume / 100ul saline. The samples were dissociated with a gentleMACS Octo d...
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