The present invention provides a medicinal composition containing a T cell population that exhibits an excellent antigen specificity and has genetic diversity, and a method for preventing or treating cancer using the medicinal composition.

The present application relates to a chimeric antigen receptor (CAR) which comprises a target-dependent on-switch CAR. The CAR of the invention may reduce cytotoxicity towards normal cells and improve CAR-T safety. CAR molecules were designed using the transmembrane and juxtamembrane motifs of the IL2 receptor β chain (IL2Rβ or IL2Rb), the L ow-Density Lipoprotein Receptor (LDLR), the Seizure 6-like Protein 2 (SEZ6L2), and degradation sequence (PSKFFSQL) of IL2Rβ, which resulted in greatly reduced CAR expression at the cell surface in the absence of target antigen, while retaining downstream activation ability in response to antigen-expressing target cells. In the absence of target antigen, CAR surface expression is undetectable. The present application has shown that primary T cells expressing these surface-unstable CAR variants are able to elicit antigen-dependent target cell killing. By limiting CAR activity in this way, the present application can reduce therapeutic toxicity and T cell exhaustion. Due to its limited detectability in the absence of antigen, the present application refers to this system as a “Stealth CAR”. The present application further relates to compositions, preparation methods and uses of the Stealth CAR of the present application.

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.

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.

The present invention is directed to chimeric antigen receptor (CAR) compositions and methods of their use in cancer and anti-viral immunotherapy. In particular, the CAR of the invention comprises a costimulatory signal (CSS) domain comprising herpes virus entry mediator protein (HVEM) or a functional fragment or variant thereof. CARs comprising such a HVEM CSS exhibit enhanced effector function.

Single-domain antibodies that bind the severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) spike protein are disclosed. The single-domain antibodies include binding domains that bind epitopes of the Spike ectodomain inside and outside the receptor binding domain. The single-domain antibodies can be used for multiple purposes including in the research, diagnosis, and prophylactic or therapeutic treatment of COVID-19.

Cellular vaccine platforms, such as vaccine immune viral opsonization platforms, for eliciting host immune responses are disclosed. Also disclosed are the methods of making and using the cellular vaccine platforms in stimulating host immune responses.

Described herein are immune cells comprising: a T-cell receptor (TCR) and a chimeric stimulating receptor (CSR) that comprises (i) a ligand-binding module that is capable of binding or interacting with a target ligand; (ii) a transmembrane domain; and (iii) a CD30 costimulatory domain, in which the CSR in the immune cells lacks a functional primary signaling domain. Also provided herein are methods of using the same or components thereof (e.g., the CSR) for therapeutic treatment of cancers (e.g., solid tumor cancers).

Described are novel immunosuppressant drug resistant armored (IDRA) T cells that co-express an exogenous T cell receptor (TCR) and one or more exogenous inhibitors of an immunosuppressant. The TCR can bind to an antigen expressed by a tumor cell or virally infected cell. Also described are methods of producing the modified T cell, and methods of treating a subject using the modified T cells.

Provided are a tandem epitope polypeptide vaccine for novel coronavirus and use thereof. Specifically, a vaccine polypeptide for novel coronavirus pneumonia is provided on the basis of analysis and study of the RBD sequence and structural information of the S protein of SARS-CoV-2. Said vaccine polypeptide comprises the following elements connected in series: a generic Th epitope sequence, a B cell epitope sequence and a T cell epitope sequence. The B cell epitope and the T cell epitope have an amino acid sequence from the RBM region of the S protein of SARS-CoV-2. Provided are a vaccine composition containing said vaccine polypeptide and use thereof. Experiments show that the vaccine polypeptide of the present invention can enable cynomolgus monkeys to initiate strong cellular and humoral immunity, and to generate neutralizing antibodies that block the binding of RBD and ACE2, and can be used for preventing and treating novel coronavirus pneumonia.