A room temperature injectable thermo-responsive hydrogel comprises a P407 poloxamer base hydrogel, chitosan, 2-Hydroxypropyl β-cyclodextrin and genipin. The chitosan and genipin form an interpenetrating scaffold within the hydrogel in which the chitosan is crosslinked with genipin. Chemotherapeutic drugs can be added to the hydrogel singly or in combination in effective amounts without any loss of thermo-responsiveness in the hydrogel. Therapeutic use of the thermo-responsive hydrogel in the intratumoural treatment of solid cancer is also described.

A room temperature injectable thermo-responsive hydrogel comprises a P407 poloxamer base hydrogel, chitosan, 2-Hydroxypropyl β-cyclodextrin and genipin. The chitosan and genipin form an interpenetrating scaffold within the hydrogel in which the chitosan is crosslinked with genipin. Chemotherapeutic drugs can be added to the hydrogel singly or in combination in effective amounts without any loss of thermo-responsiveness in the hydrogel. Therapeutic use of the thermo-responsive hydrogel in the intratumoural treatment of solid cancer is also described.

The disclosure provides compounds of Formula 1, and the pharmaceutically acceptable salts thereof. The variables in Formula 1, e.g. X.sup.1-X.sup.5, A.sup.1, A.sup.2, and R.sup.1-R.sup.4 are described herein. Such compounds are useful as prostaglandin transport (PGT) inhibitors. The disclosure further includes pharmaceutical compositions comprising a compound of Formula 1 or salt thereof and methods of using compounds of Formula 1 and salts thereof to treat diseases and disorders mediated, at least in part, by prostaglandin levels or cyclooxygenase activity. Such diseases and disorders include painful and inflammatory conditions.

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Disclosed is a humanized 4-1BB monoclonal antibody, an antigen-binding fragment thereof, a pharmaceutical composition and a medical use thereof. The monoclonal antibody comprises CDR1 with the amino acid sequence shown in SEQ ID NO: 1 or SEQ ID NO: 4, CDR2 with the amino acid sequence shown in SEQ ID NO: 2 or SEQ ID NO: 5, CDR3 with the amino acid sequence shown in SEQ ID NO: 3, CDR1′ with the amino acid sequence shown in SEQ ID NO: 6, CDR2′ with the amino acid sequence shown in SEQ ID NO: 7, CDR3′ with the amino acid sequence shown in SEQ ID NO: 8. The monoclonal antibody binds to human 4-1BB with high affinity and specificity, leads to a significant increase in T cell proliferation and TNF-γ production, and enhances and stimulates human 4-1BB-mediated immune response.

Disclosed is a humanized 4-1BB monoclonal antibody, an antigen-binding fragment thereof, a pharmaceutical composition and a medical use thereof. The monoclonal antibody comprises CDR1 with the amino acid sequence shown in SEQ ID NO: 1 or SEQ ID NO: 4, CDR2 with the amino acid sequence shown in SEQ ID NO: 2 or SEQ ID NO: 5, CDR3 with the amino acid sequence shown in SEQ ID NO: 3, CDR1′ with the amino acid sequence shown in SEQ ID NO: 6, CDR2′ with the amino acid sequence shown in SEQ ID NO: 7, CDR3′ with the amino acid sequence shown in SEQ ID NO: 8. The monoclonal antibody binds to human 4-1BB with high affinity and specificity, leads to a significant increase in T cell proliferation and TNF-γ production, and enhances and stimulates human 4-1BB-mediated immune response.

A nanomedicinal composition comprising a nanocarrier and a pharmaceutical agent mixture comprising an anti-cancer therapeutic and an antioxidant. The nanocarrier comprises a porous silicate matrix and particles of a magnetic ferrite disposed in the pores of the porous silicate matrix. The pharmaceutical agent mixture is disposed in the pores and/or on the surface of the nanocarrier by a solution phase impregnation process. The nanomedicinal composition is used in a method of treating breast cancer.

A nanomedicinal composition comprising a nanocarrier and a pharmaceutical agent mixture comprising an anti-cancer therapeutic and an antioxidant. The nanocarrier comprises a porous silicate matrix and particles of a magnetic ferrite disposed in the pores of the porous silicate matrix. The pharmaceutical agent mixture is disposed in the pores and/or on the surface of the nanocarrier by a solution phase impregnation process. The nanomedicinal composition is used in a method of treating breast cancer.

The addition of a selective, fast-acting, short half-life CDK 4/6 inhibitor in a very specific dosage regimen to the combination of chemotherapy with a checkpoint inhibitor provides superior results in the treatment of a tumor or cancer. The unexpected discovery is that the short pulsatile specifically-timed administration of a selective, fast-acting, short half-life CDK 4/6 inhibitor during administration of the chemotherapy portion of the triple combination therapy has a profound effect on the immune cells in the cancer microenvironment.

The addition of a selective, fast-acting, short half-life CDK 4/6 inhibitor in a very specific dosage regimen to the combination of chemotherapy with a checkpoint inhibitor provides superior results in the treatment of a tumor or cancer. The unexpected discovery is that the short pulsatile specifically-timed administration of a selective, fast-acting, short half-life CDK 4/6 inhibitor during administration of the chemotherapy portion of the triple combination therapy has a profound effect on the immune cells in the cancer microenvironment.

The addition of a selective, fast-acting, short half-life CDK 4/6 inhibitor in a very specific dosage regimen to the combination of chemotherapy with a checkpoint inhibitor provides superior results in the treatment of a tumor or cancer. The unexpected discovery is that the short pulsatile specifically-timed administration of a selective, fast-acting, short half-life CDK 4/6 inhibitor during administration of the chemotherapy portion of the triple combination therapy has a profound effect on the immune cells in the cancer microenvironment.