The present disclosure provides an allogeneic whole cell cancer vaccine platform that includes compositions and methods for treating and preventing breast cancer. Provided herein are compositions containing a therapeutically effective amount of cells from one or more cancer cell lines, some or all of which are modified to (i) inhibit or reduce expression of one or more immunosuppressive factors by the cells, and/or (ii) express or increase expression of one or more immunostimulatory factors by the cells, and/or (iii) express or increase expression of one or more tumor-associated antigens (TAAs), including TAAs that have been mutated, and which comprise cancer cell lines that natively express a heterogeneity of tumor associated antigens and/or neoantigens, and/or (iv) express one or more tumor fitness advantage mutations, including but not limited to driver mutations. Also provided herein are methods of making and preparing the breast cancer vaccine compositions and methods of use thereof.

In one aspect, the present invention provides a method for treating cancer comprising tumor cell vaccination in combination with hematopoietic and immune cell transplantation. In some embodiments, the method involves autologous tumor cell vaccination prior to autologous hematopoietic and immune cell transplantation. In another aspect, the present invention provides a method of purifying tumor cells from a subject in preparation for vaccination.

The present disclosure provides methods and compositions for enhancing the immune response toward cancers and pathogens. It relates to an immunoresponsive cell comprising an antigen-recognizing receptor (e.g., a chimeric antigen receptor (CAR) or a T cell receptor (TCR)), and expressing increased level of IL-36. In certain embodiments, the engineered immunoresponsive cells are antigen-directed and have enhanced immune-activating properties.

Combination therapies comprising a microorganism and an immune modulator, and methods of modulating and treating cancers are disclosed.

The described invention provides allogeneic tumor cell vaccines comprising tumor cell lines or tumor cell line variants that are genetically engineered to express a core group of three immunomodulatory molecules, and optionally additional R immunomodulatory polypeptides for induction of one or more subpopulations of PBMCs to proliferate in response to the expressed immunomodulatory molecules and to then enter an effector phase for killing of tumor cells. According to some embodiments, the tumor cell vaccine candidate can induce an immune response in the recipient cancer patient that cross reacts with the patient's own (autologous) tumor cells, the effects of which are sufficient to result in enhanced anti-tumor immunity contributing to the increased survival of a vaccinated patient cohort compared to a matched unvaccinated patient cohort.

The presently described subject matter relates to cancer vaccines composed of the signal peptide domain of tumor associated antigens or proteins. The described peptide vaccines have multiple MHC class I and class II epitopes which are highly abundant in the population. Therefore, these vaccines induce a strong, comprehensive immune response against the target proteins in the majority of the vaccinated population, and thereby induce an immune reaction against tumors expressing such target proteins. Specifically, the presently described subject matter relates to peptide vaccines composed of the signal peptide domain of Mucin (MUC1), BAGE-1 or ARMET, and their use for the treatment of cancers which express Mucin (MUC1), BAGE-1 or ARMET.

There are disclosed inter alia polypeptides and nucleic acids encoding said polypeptides which are useful in the treatment, prevention and diagnosis of cancer, particularly melanoma, especially cutaneous melanoma and uveal melanoma.

Described herein are novel vaccine compositions and methods for use thereof in inducing an immune response in a subject especially aged subjects. Specifically exemplified are vaccine compositions that include an antigen; a cyclic dinucleotide; soluble tumor necrosis factor (TNF); or a CD64 antibody or antibody fragment. Optionally, the vaccine composition comprises a TNF conjugated with a moDC targeting moiety in addition to or in place of TNF or CD64 antibody or antibody fragment, or both TNF and CD64 antibody or antibody fragment.

The invention provides methods of modulating follicular regulatory T (TFR) cell-mediated immune responses and the use of those methods in the treatment of diseases or conditions such as viral, bacterial, pathogenic, or fungal infections or cancer. Such methods provide for boosting of antibody production through the use of IL-21 to overcome TFR cell suppression of antibody production.

Disclosed herein are compositions and methods for cancer immunotherapy, and more particularly immune cells loaded with protein clusters and/or immunostimulatory fusion molecules (IFMs), in combination with an inhibitor of a checkpoint inhibitor.