Methods and materials for treating cancer (e.g., melanoma) in a subject and for improving efficacy of adoptive immune cell therapy are described. The methods can include administering immune cells (e.g., chimeric antigen receptor T cells or tumor-infiltrating lymphocytes) having reduced expression of a VPS39 polypeptide to the subject.

The present invention provides methods for isolating and cryopreserving tumor infiltrating lymphocytes (TILs) and producing therapeutic populations of TILs, including methods via use of a kit and a semi-automatic device for aseptic disaggregation, enrichment, and cryopreservation of a resected tumor prior to expansion of the TIL population. The present invention also provides methods for expansion, and/or stabilization of TILs, for instance UTILs, compositions involving the same and methods of treatment involving the same.

Disclosed is a genetically modified oncolytic herpes simplex virus (oHISV) encoding a truncated nonsignaling variant of at least one tumor associated/specific antigen, and at least one chemokine. The expression of the truncated nonsignaling variant and the chemokine is under the control of an immediate-early gene promoter of HSV, and the truncated nonsignaling variant is expressed and presented on a tumor cell surface as a biomarker upon replication of the oHSV in the tumor cell, and the chemokine is expressed and released to induce chemotaxis of an immune cell towards the tumor cell. The genetically modified oHSV can be used in combination with CAR-T, ADC, and/or BiTE therapies.

Provided herein are TILs that are (i) CD39.sup.LO/CD69.sup.LO and/or CD39/CD69 double negative, (ii) CD39/CD69 double knock-out, or (iii) the combination of (i) and (ii). In some embodiments, the subject TILs are produced by genetically manipulating a population of TILs that have been selected for (i) CD39.sup.LO/CD69.sup.LO and/or CD39/CD69 double negative, (ii) CD39/CD69 double knock-out, or (iii) the combination of (i) and (ii) expression (e.g, a (i) CD39.sup.LO/CD69.sup.LO and/or CD39/CD69 double negative, (ii) CD39/CD69 double knock-out, or (iii) the combination of (i) and (ii) enriched TIL population). Also provided herein are expansion methods for producing such genetically modified TILs and methods of treatment using such TILs.

Disclosed is an isolated or purified T cell receptor (TCR), wherein the TCR has antigenic specificity for a mutated human RAS amino acid sequence with a substitution of glutamine at position 61 with lysine. Related polypeptides and proteins, as well as related nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions are also provided. Also disclosed are methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal.

Provided herein are a recombinant chimeric antigen receptor (CAR) fusion protein, a method of modifying an immune cell into a CAR immune cell by treating the immune cell with the recombinant CAR fusion protein, and a method of treating cancer by administering the CAR immune cell to a subject in need thereof.

A method of treating cancer in a subject is disclosed. The method comprises administering to the subject a therapeutically effective amount of a population of T cells, wherein an alpha chain of a TCR of at least 10% of the T cells of the population has a CDR3 amino acid sequence as set forth in SEQ ID NO: 6, and a beta chain of the CDR has a CDR3 amino acid sequence as set forth in SEQ ID NO: 7.

The present invention provides recombinant TIM-4 fusion proteins comprising an extracellular domain of TIM-4 and at least one co-stimulatory domain. Also provided are cells comprising the fusion protein and methods of making and using the same.

A polypeptide comprising the sequence of SEQ. ID NO. 2, 3, 4, 7 or 8. The polypeptide may have the sequence of an immunogenic fragment thereof comprising at least eight amino acids, wherein the immunogenic fragment is not one of SEQ. ID NOS. 6 or 11 to 16. The polypeptide may have a sequence having at least 80% sequence identity to the aforementioned polypeptide or immunogenic fragment. The polypeptide is less than 100 amino acids in length and does not comprise the sequence of any of SEQ. ID NOS. 10, 46, 56, 57 or 59 to 62 and does not consist of the sequence of SEQ ID NO. 58. The polypeptide is useful in the treatment or prophylaxis of cancer.

The invention provides a chimeric antigen receptor (CAR) having antigenic specificity for CD70, the CAR comprising: an antigen bindingtransmembrane domain comprising a CD27 amino acid sequence lacking all or a portion of the CD27 intracellular T cell signaling domain; a 4-1BB intracellular T cell signaling domain; a CD3? intracellular T cell signaling domain; and optionally, a CD28 intracellular T cell signaling domain. Nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions relating to the CARs are disclosed. Methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal are also disclosed.