The present invention provides compositions and methods for treating a patient having cancer, as well as methods for potentiating an immune checkpoint inhibitor therapy. The methods comprise administering larazotide or a derivative thereof to a subject in need, including subjects undergoing checkpoint inhibitor therapy, and subjects scheduled to undergo immune checkpoint inhibitor therapy.

The present disclosure is directed to antibodies directed against CD4, compositions thereof, and methods employing such compositions for the prevention, treatment, and/or functional cure of HIV infection. The disclosed antibodies exert potent competitive HIV entry inhibition by binding to domain 1 of CD4 in both cell-free and cell-to-cell systems. The disclosed antibodies also inhibit antigen induced T cell proliferation and cytokine production (IL2 and IFN-gamma) of CD4+ T cells, which is implicated in the pathogenic cycle of pyroptosis. The disclosed antibodies also have the ability to reactivate resting CD4+ T cells, which is particularly useful for reactivating latent reservoirs of HIV in resting T cells to make these cells susceptible to treatment with antiretroviral agents. Reactivation of HIV infected resting CD4+ T cells allows combinational treatment incorporating antibodies of the current invention with HAART in HIV infected patients leading to the functional cure of HIV.

Provided herein are lipid particles containing a lipid bilayer enclosing a lumen or cavity, a henipavirus F protein molecule or biologically active portion thereof, and a targeted envelope protein containing a henipavirus envelope attachment glycoprotein G (G protein) or biologically active portion thereof and a binding domain, such as a single domain antibody (sdAb) variable domain. Also provided herein are targeted envelope proteins containing a G protein fused or linked to a binding domain, such as a sdAb variable domain, and polynucleotides encoding such proteins. Also provided are producer cells and compositions containing such targeted lipid particles and methods of making and using the targeted lipid particles.

A “nanolipogel” is a delivery vehicle including one or more lipid layer surrounding a hydrogel core, which may include an absorbent such as a cyclodextrin or ion-exchange resin. Nanolipogels can be constructed so as to incorporate a variety of different chemical entities that can subsequently be released in a controlled fashion. These different incorporated chemical entities can differ dramatically with respect to size and composition. Nanolipogels have been constructed to contain co-encapsulated proteins as well as small hydrophobic drugs within the interior of the lipid bilayer. Agents incorporated within nanolipogels can be released into the milieu in a controlled fashion, for example, nanolipogels provide a means of achieving simultaneous sustained release of agents that differ widely in chemical composition and molecular weight. Additionally, nanolipogels can favorably modulate biodistribution.

A cancer therapeutic agent according to an embodiment of the present invention contains, as active ingredients, IL-18 and one or more antibodies selected from the group consisting of an anti-PD-L1 antibody, an anti-PD-1 antibody, an anti-PD-L2 antibody, an anti-CTLA-4 antibody, an anti-CD25 antibody, an anti-CD33 antibody, and an anti-CD52 antibody.

The present invention relates, in part, to certain cancer biomarkers and use thereof in methods for treating cancer, such as in evaluating and/or predicting patient responses to treatment with a CXCR4 inhibitor optionally in combination with a immunotherapeutic agent, in patients with a cancer such as melanoma, including resectable and unresectable melanoma. The present invention also provides a biomarker expression platform, which is a combination of a set of genes or biomarkers that are correlated with response to a CXCR4 inhibitor in a tumor as well as a normalization gene set. A method and system of using the biomarker expression platform to derive biomarker signatures of anti-tumor response and to test patient samples for predictive biomarker signatures are also disclosed.

Disclosed is a means for reducing side effects of an immune checkpoint regulator that is used as an anticancer drug or the like. A side-effect reducing agent according to the present invention comprises as an effective ingredient an anti-CD4 antibody having a high cytotoxic activity, or an anti-CD4 antibody or antigen-binding fragment thereof which antibody or fragment comprises a cytotoxic component bound thereto. The anti-CD4 antibody is a human-type chimeric antibody, humanized antibody or human antibody against human CD4. The immune checkpoint regulator may be, for example, an anti-PD-L1 antibody, an antagonistic anti-CTLA-4 antibody, or an agonistic anti-OX40 antibody.

The invention relates to compositions comprising a CD4 lymphocyte depleting agent; and methods of using the compositions to treat, prevent, reduce the severity of and/or slow the progression of a condition in a subject. The invention also relates to use of combinations of a CD4 lymphocyte depleting agent and at least one additional agent to treat, prevent, reduce the severity of and/or slow the progression of a condition in a subject. The additional agent may be an immune check point inhibitor, an adoptive immune therapeutic, an immune adjuvant, or an immune modulating agent, or their combinations.

The present invention relates to the treatment of cancer and to the prevention of cancer growth and/or metastasis. In particular, the invention relates to cellular and acellular vaccines containing C3d, a proteolytic product of complement (C3), and methods of enhancing a host immune response (e.g., a T cell mediated immune response) against cancers using same. Compositions and methods of the invention find use, alone or in conjunction with other cancer therapies, in treating lymphoma and/or cancers that develop and/or persist by evading host immune surveillance and/or responses (e.g., T-cell mediated immune responses). Compositions and methods of the invention find use in both clinical and research settings, for example, within the fields of biology, immunology, medicine, and oncology.

The present disclosure relates to a fusion protein and uses thereof. For example, the fusion protein comprises an extra-cellular domain, a transmembrane domain, and an intracellular domain. The extracellular domain is derived from a first molecule, and the intracellular domain is derived from a second molecule. The first molecule is different from the second molecule, and the second molecule comprises OX40, CD40, 4-1 BB, GITR, ICOS, CD28, CD27, HER2, EGFR, EL-10R, IL-12R, IL-18R1, IL-23R, GP130, or IL-15Ra.