Provided are methods for treating a solid cancer in a subject by administering an effective amount of a radioconjugated CCR8-targeting agent to deplete tumor-associated CCR8-positive Treg cells, alone or in combination with one or more additional therapeutic agents or modalities, such as a radioconjugated CD33-targeting agent.

The chimeric antigen receptor that recognizes CCR8 as an antigen of the present invention has cytotoxic activity against CCR8-expressing cells by being expressed in effector cells.

The present invention provides a universal, yet adaptable, anti-tag chimeric antigen receptor (AT-CAR) system which provides T cells with the ability and specificity to recognize and kill target cells, such as tumor cells, that have been marked by tagged antibodies. As an example, ?FITC-CAR-expressing T cells have been developed that specifically recognize various human cancer cells when those cells are bound by cancer-reactive FITC-labeled antibodies. The activation of ?FITC-CAR-expressing T cells is shown to induce efficient target lysis, T cell proliferation, and cytokine/chemokine production. The system can be used to treating subjects having cancer.

An isolated antigen-binding protein may be capable of binding to CLDN18.2. Such an isolated antigen-binding protein may include HCDR1, HCDR2, and/or HCDR3. The HCDR1 may include an amino acid sequence as set forth in any one of SEQ ID NO: 2, SEQ ID NO: 10, and SEQ ID NO: 16. The HCDR2 may include an amino acid sequence as set forth in SEQ ID NO: 68 or SEQ ID NO: 11. The HCDR3 may include an amino acid sequence as set forth in SEQ ID NO: 67. A chimeric antigen receptor may include the isolated antigen binding protein. A method may make such an antigen-binding protein and an antigen binding protein and the chimeric antigen receptor may be derived from the isolated antigen-binding protein.

A chimeric antigen receptor targeting an oncolytic virus-derived protein, an immune cell expressing the same, and uses thereof are disclosed. The chimeric antigen receptor-expressing immune cell can effectively target the protein A56 that is specifically expressed on the cancer cell surface, which enables targeted therapy for cancer cells that have survived even infection with an oncolytic virus, thereby providing effective anticancer therapy. The chimeric antigen receptor-expressing immune cell can have increased activation and proliferation capacity specifically for protein A56 and exhibit excellent cytotoxic effects, thereby providing effective anticancer therapy against protein A56-expressing cancer cells. The immune cell is preferably used in combination with an oncolytic virus, and may be additionally used in combination with a drug capable of enhancing an anticancer effect of the oncolytic virus (for example, hydroxyurea, chemotherapeutic agents for regulating lymphocyte removal (for example, cyclophosphamide and fludarabine), or immunotherapeutic agents).

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.

Disclosed herein are compositions and methods for enhancing T-cell activity by modulating a miRNA so as to improve T-cell therapies, infectious disease therapies and down-regulate auto-immune responses.

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.

Isolated pluralities of T cells which recognize at least one epitope of an intestinal cancer antigen or CNS cancer antigen and pharmaceutical compositions comprising the same are disclosed. Methods of making a plurality of T cells that recognize at least one epitope of an intestinal cancer antigen or CNS cancer antigen are also disclosed. Methods of treating an individual who has been diagnosed with cancer of a mucosal tissue or preventing such cancer in an individual at elevated risk are disclosed as are nucleic acid molecules that comprise a nucleotide sequence that encode proteins that recognize at least one epitope of an intestinal cancer antigen or CNS cancer antigen and T cells comprising such nucleic acid molecules.

The present invention relates to compositions and methods variously useful in treating cancer, inhibiting graft rejection, and treating autoimmune disease. The compositions and methods include those in which macrophages are conditioned to down regulate or upregulate the expression or activity of SIRP? or its interaction with CD47.