Disclosed herein are methods of treating a subject exhibiting a solid tumor that expresses Glypican-3 (GPC3). The methods typically utilize g GPC3 chimeric antigen receptor immunoresponsive cells to a subject in need thereof to effect killing of tumor cells.

The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.

Some embodiments of the present disclosure are directed to methods that include delivering to a subject a nucleic acid encoding an antigen, wherein the nucleic acid is delivered via a tumor-selective vehicle or via intratumoral injection, and delivering to the subject an immune cell expressing a receptor that binds to the antigen.

Provided herein are CAR-T compositions that are directed to GPC3, including a chimeric receptor, and engineered immune cells to GPC3. The disclosure also provides vectors, compositions, and methods of treatment using GPC3 antigen binding molecules and engineered immune cells, optionally in combination with expression of IL-18. GPC3 CAR compositions provided herein can be used for the treatment of certain cancers.

The present application provides GPC2-specific antibodies and antigen binding fragments thereof. A chimeric antigen receptor (CAR) that specifically binds glypican-2 (GPC2) comprising a GPC2-specific antibody, a transmembrane domain, and an intracellular signaling domain. T cells comprising the disclosed CAR constructs can be used for cancer immunotherapy.

It is disclosed herein that condroitin sulfate proteoglycan 4 (CSPG4), also known as high molecular weight melanoma associated antigen, is overexpressed on basal breast carcinoma cells (BBC), specifically triple negative basal breast carcinoma cells (TNBC). Methods for detecting basal breast cancer in a subject are disclosed. Methods are also disclosed for inhibiting the growth of a basal breast cancer cell. These methods include contacting the basal breast cancer cell with an effective amount of an antibody that specifically binds CSPG4. Additional treatment methods, and the use of antibody panels, are also described herein.

Disclosed herein are genetically engineered hematopoietic cells (e.g., genetically engineered hematopoietic stem cells, or genetically engineered immune cells), which co-express one or more co-stimulatory polypeptides with an anti-GPC3 chimeric antigen receptor (CAR), and uses thereof for enhancing T cell anti-tumor activity in a subject in need of the treatment.

The present invention relates to an immune effector cell which expresses a chimeric antigen receptor targeting GPC3 and exogenous IL12. The present invention further provides a pharmaceutical composition containing the immune effector cell and a method for treating tumor, particularly GPC3 positive tumor by using the immune effector cell or the pharmaceutical composition. The immune effector cell in the present invention is effective to an entity tumor cell in vitro, and is outstanding in effect of extinguishing the entity tumor cell in vivo.

Disclosed are compositions of matters, cells, and treatment protocols useful for induction of anticancer responses in a patient suffering from cancer. In one embodiment the invention provides the use of NR2F6 silencing or gene editing in cord blood cells possessing anti-tumor activity in order to induce potentiated killer cells suitable for therapeutic use. In one embodiment said allogeneic cord blood killer cells are administered to initiate a cascade of antitumor immune responses, with initially responses mediated by allogeneic killer cells, and followed by endogenous immune responses.

Embodiments of the disclosure include compositions and methods effective for immunotherapy, such as for cancer. The embodiments include cells that recognize a combination of two signals or three signals present at the tumor microenvironment. In certain embodiments, the signals for antigen stimulation, co-stimulation, and cytokine signaling act through separate molecules, although in certain embodiments the signals for antigen stimulation and co-stimulation are transmitted through the same molecule.