Methods for treating a CD30-positive cancer in a subject are disclosed, wherein the methods comprise administering a lymphodepleting chemotherapy and CD30-specific chimeric antigen receptor (CAR)-expressing cells.

Herein are provided anti-CD22 single domain antibodies (sdAb) prepared by immunizing a llama with the extracellular domain of the predominant human CD22 isoform. By constructing a library of the heavy chain repertoire generated, VHH antibodies specific to the immunogen were isolated. The 27 example antibodies initially produced comprise CDR1, CDR2, and CDR3 sequences corresponding, respectively to SEQNOs: 1-3, 4-6, 7-9, 10-12, 13-15, 16- 18, 19-21, 22-24, 25-27, 28-30, 31-33, 34-36, 37-39, 40-42, 43-45, 46-48, 49-51, 52-54, 55- 57, 58-60, 61-63, 64-66, 67-69, 70-72, 73-75, 75-78, and 79-81; and related sequences. Also provided are multivalent antibodies comprising any one of the sdAbs, including bispecific T-cell engagers, bispecific killer cell engagers (BiKEs), and trispecific killer cell engagers (TriKEs). Also described are chimeric antigen receptors (CARs) for CAR-T therapy comprising any one of the aforementioned sdAbs. Uses of these molecules in the treatment of cancer are also described.

Provided herein are systems and methods for identifying alternative splicing derived cell surface antigens. Also provided are methods and compositions for using the identified cell surface antigens. Further provided are methods, compositions, and systems for diagnosing diseases in a subject using the identified cell surface antigens or treating diseases using the same.

The present disclosure provides chimeric cytokine receptors comprising an intracellular signaling domain of an interleukin-9 receptor alpha (IL9Ra). The present disclosure also provides modified cell(s), i.e., immune cell(s) or precursor cell(s) thereof, wherein the cell(s) are engineered to express a) interleukin-9 receptor alpha (IL9Ra), or a chimeric cytokine receptor disclosed herein; and b) a chimeric antigen receptor (CAR). The present disclosure further provides a vector (e.g., an oncolytic adenoviral vector) comprising a nucleic acid sequence encoding a cytokine, as well as methods of using the modified cells and the vector for treating cancer in a subject in need thereof. Also provided are modified immune cell(s) or precursor cell(s) thereof which are engineered to express a chimeric antigen receptor (CAR), wherein expression of Cullin 5 in the cell(s) is reduced and/or eliminated. Also provided are methods and uses of the modified cells, e.g., for treating at least one sign and/or symptom of cancer. Related nucleic acids, vectors, and pharmaceutical compositions are also provided.

The present application relates to an attenuated oncolytic virus strain, an oncolytic virus vaccine and a drug for treating tumors by combining the oncolytic virus vaccine with immune cells. The present application provides a new attenuated oncolytic virus strain by a site-directed mutation of a matrix protein M of a VSV wild-type virus. On the basis of the attenuated oncolytic virus strain, the present application further provides a vaccine that can be used in tumor treatment. On the basis of the vaccine, the present application further provide a drug that can effectively treat multiple kinds of tumors by combining the vaccine with immune cells.

The present invention provides a method for treating a solid cancer which comprises the step of administering a cell to a subject, wherein the cell comprises a nucleic acid sequence encoding interleukin 12 (IL-12) downstream of a frame-slip motif (FSM) or a translational readthrough motif (TRM).

A T cell antigen receptor, an immune cell for expressing the T cell antigen receptor (TCR) and a preparation method and use thereof. The TCR disclosed in the present invention can be specifically activated by virus antigen peptide presenting cells, so that the release level of extracellular cytokines IFNγ and IL2 and the release amount of lactate dehydrogenase are improved, and target cells are significantly killed.

Provided is a T lymphocyte. The T lymphocyte co-expresses a fusion protein and a chimeric antigen receptor, and the chimeric antigen receptor identifies a tumor antigen, herein the chimeric antigen receptor includes: an extracellular region; a transmembrane region, herein the transmembrane region is connected to the extracellular region, and embedded into a cell membrane of a transgenic lymphocyte; and an intracellular region, herein the intracellular region is connected to the transmembrane region, and the intracellular region includes an immune co-stimulatory molecule intracellular segment. The fusion protein includes: an immune checkpoint single-chain antibody and a T cell activation molecule.

The present invention aims to increase cytotoxic activity of an immunocompetent cell to thereby enhance a therapeutic effect against diseases such as cancers, and provides an immunocompetent cell having decreased diacylglycerol kinase activity, which cell expresses a fusion protein including IL-15 and an IL-15 receptor α subunit, and which cell expresses a chimeric antigen receptor.

The invention involves generating a T cell response to subdominant antigens and using the cells to therapeutically change the cellular homeostasis and nature of the immune response. In a preferred embodiment, the cells are generated outside of the patient avoiding the influence of the patient's immunologic milieu. By stimulating and growing the T cells from a patient in a tissue culture to one or more subdominant antigens and the transplanting them into the patient, if enough cells are expanded and transplanted, the transplanted cells overwhelm the endogenous dominant T cells in the response to either break or induce immune tolerance or otherwise modify the immune response to the cells or organism expressing that antigen. When the memory cells are established they are then reflective of this new immunodominance hierarchy so that the desired therapeutic effect is long lasting. In effect, the transplantation exogenously generated T cells reactive to the subdominant antigens is recapitulating priming and rebalancing the patient's immune response to target previously subdominant antigens in the cells or organism to produce a therapeutic benefit.