Systems and methods for identifying neoantigen peptide candidates are described. Such systems and methods can be used to generate engineered immune cells that target neoantigen peptides. In certain embodiments, the systems and methods do not require in silico epitope binding prediction algorithms. In certain embodiments, neoantigens are identified for a cancer or tumor with a low mutational burden.

The present disclosure relates to methods of treating cancer or preventing metastases of a cancer in a subject in need thereof. The disclosure further relates to compositions comprising a heterogeneous population of T cells with reactivity to individualized cancer epitopes, or neoantigens, that are useful for adoptive immunotherapy and methods for making such T cell compositions.

Novel nucleic acid sequences, vectors, modified cells, peptides and pharmaceutical compositions are provided that are useful in the treatment of human subjects having a NPM1 positive haematological malignancy. Corresponding methods and uses are also provided.

The present disclosure provides tumor neoantigenic peptide sequences and nucleotide sequences encoding such peptide sequences; a vaccine or immunogenic composition capable of raising a specific T-cell response comprising one or more of the neoantigenic peptides, or comprising nucleic acid encoding one or more of the neoantigenic peptides; an antibody, or an antigen-binding fragment thereof, a T cell receptor (TCR), or a chimeric antigen receptor (CAR) that specifically binds such neoantigenic peptides; methods of producing such antibodies, TCRs or CARs; polynucleotides encoding such neoantigenic peptides, antibodies, CARs or TCRs, optionally linked to a heterologous regulatory control sequence; immune cells that specifically bind to such neoantigenic peptides; and dendritic cells or antigen presenting cells that have been pulsed with one or more of the neoantigenic peptides; and methods of using such products in particular therapeutic uses of these products.

Disclosed herein is a system and methods for determining the alleles, neoantigens, and vaccine composition as determined on the basis of an individual's tumor mutations. Also disclosed are systems and methods for obtaining high quality sequencing data from a tumor. Further, described herein are systems and methods for identifying somatic changes in polymorphic genome data. Finally, described herein are unique cancer vaccines.

The present disclosure relates to methods for profiling subject specific and personalized T cell receptor (TCR) repertoires using a single-cell sequencing method. More particularly, disclosed are methods for determining binding of T cell receptors to subject specific neoantigens. In addition, the techniques herein may identify the antigenic targets of T cell receptors in the context of tumor neoantigens. Moreover, the present disclosure enables the discovery of T cell targets in numerous diseases, with implications for understanding the basic mechanisms of the mammalian immune response and for developing antigen-specific diagnostic markers and therapies. Finally, cloned TCRs can be used to formulate personalized immunotherapies for those inflicted with a disease, such as cancer.

Disclosed in the present application are the use of an antigen short peptide in screening a drug for treating HPV-related diseases and a TCR screened by same, wherein the amino acid sequence of the antigen short peptide is as shown in SEQ ID NO: 1 or SEQ ID NO: 2. In the present application, the antigen short peptide can be used to screen a specific T cell receptor (TCR), and the T cell transduced with the TCR can be specifically activated and have a very strong killing effect on tumor cells expressing A1101 and HPV, which can be used for immunotherapy of HPV positive tumors, such as cervical cancer. In addition, the T cell transduced with the TCR of the present application has a strong activation reaction on a cell line expressing E6, has no activation reaction on a cell line not expressing E6, and has a very strong killing function on the cell line expressing E6 and can effectively inhibit the growth of E6 positive tumors.

As disclosed herein, SIRP is integral to immuno-evasion by many different cancer types as well as cancer resistance to therapies, and reducing SIRP levels on can bolster antigen acquisition, processing, and presentation, decrease TME immunosuppression and thereby promote tumor-specific T cell activation to eliminate tumors and generate an adaptive immune response consisting of memory T cells, circulating antibodies, and plasma cells, all of which may be specific for neo-antigens in the original cancer. Therefore, disclosed are activated SIRP.sup.low macrophages that are useful for treating cancers.

A cancer vaccine technology is provided which knocks out expression of cell surface immune checkpoint proteins, to facilitate their processing by immune cells, and optionally by knocking-in the expression of cytokines to boost immune response. Non-replicating tumor cells lacking cell surface CD47 are highly effective immunizing agents against subcutaneous mouse melanoma. Whole-cell vaccines inhibited tumor growth, and immunophenotyping showed a dramatic increase in activated effector cell subsets and M1-type macrophages aided by a significant reduction in the tumor-associated macrophage and myeloid derived suppressor cell compartments. A remarkable downregulation of cell surface CD47 was observed in the tumors that did escape after vaccination with genetically modified cells, suggesting the intricate involvement of CD47 in a prophylactic situation. An effective vaccination strategy to increase tumor-specific immune response in solid tumors is provided to improve the outcome of cancer immunotherapy.

Embodiments of the disclosure concern methods and compositions related to T cell receptors directed against breast cancer neoantigens, including immunotherapeutic compositions of any kind. In specific embodiments, the TCRs are identified following particular methods of producing neoantigen-specific T cells, including particular culturing methods.