The present invention provides methods of engineering ?? T cells (e.g., v?1 T cells and v?2 T cells) by transduction with a viral vector (e.g., a viral vector with a betaretroviral pseudotype and a 5 Retroviridae family viral vector backbone). Further provided are compositions of engineered ?? T cells and methods of using the same.

In one aspect, the invention provides a transgenic non-human animal model having germ cells and somatic cells containing an endogenous MMTV-SV40-Spy1A gene sequence introduced into said animal model or an ancestor of said animal model at an embryonic stage, wherein said gene sequence comprises a mouse mammary tumor virus gene (MMTV), a functionally disrupted SV40 gene (SV40) and a human Spy1A gene. In another aspect, the present invention provides a transgenic non-human animal model whose germ cells and somatic cells contain an endogenous Spy1A-pTRE-Tight gene sequence introduced into said animal model or an ancestor of said animal model at an embryonic stage. Preferably, the Spy1A-pTRE-Tight animal model expresses the Spy1A gene and develop cancer, preferably breast cancer, when administered with tetracycline, preferably doxycycline.

Disclosed herein, in aspects, are compositions, methods, kits, and systems relating to efficient delivery of freights (e.g., therapeutic freights) into cells, for instance, for in vivo delivery.

The disclosure relates to betaretroviruses (genus Betaretrovirus), and recombinant betaretroviral envelope (rENV) protein for use in viral vector platforms, an engineered delivery vehicle and gene therapy, their associated methods of use and manufacture. In particular, the present disclosure provides compositions and methods to tune betavirus envelope proteins such that they target a particular cell surface receptor; i.e., are cell and/or tissue-type specific, allowing for better site-specific transgene delivery and expression.

The invention relates to peptides, proteins, nucleic acids, and cells for use in immunotherapeutic methods. In particular, the invention relates to the immunotherapy of cancer. The invention provides T cell receptors (TCRs), tumor infiltrating lymphocytes (TILs), and vaccines that recognize HERV-K. The invention provides TCR sequences generated from tumor infiltrating lymphocytes that recognize HERV-K antigens as peptides bound to the Major Histocompatibility Complex (MHC), resulting in an interaction between the HLA-peptide complex and the CDS TCR. Peptides bound to molecules of the MHC, or peptides as such, can also be targets of antibodies, soluble TCRs, and other binding molecules.

The present disclosure provides recombinantly manufactured fusion proteins comprising a HERV-K (HML-2) Env protein fragment or an analog thereof linked to a human Fc fragment. Embodiments include the administration of the fusion proteins to patients having a disease or a disorder with the intention of mitigating and/or reducing the duration of symptoms associated with the condition or disease (for example but not limited to muscular weakness, paralysis and respiratory failure), and/or preventing symptoms associated with the condition or disease, for example, by preventing motor neuron degeneration and cell death in ALS patients associated with the condition or disease. Accordingly, treatment generally means both therapeutic treatment and prophylactic or preventative measures. Improvement after treatment may be manifested as a decrease or elimination of such symptoms, e.g., by a decrease or elimination of symptoms associated with ALS, and/or by a decrease in the duration of such symptoms.

The present disclosure provides recombinantly manufactured fusion proteins comprising a HERV-K (HML-2) Env protein fragment or an analog thereof linked to a human Fc fragment. Embodiments include the administration of the fusion proteins to patients having a disease or a disorder with the intention of mitigating and/or reducing the duration of symptoms associated with the condition or disease (for example but not limited to muscular weakness, paralysis and respiratory failure), and/or preventing symptoms associated with the condition or disease, for example, by preventing motor neuron degeneration and cell death in ALS patients associated with the condition or disease. Accordingly, treatment generally means both therapeutic treatment and prophylactic or preventative measures. Improvement after treatment may be manifested as a decrease or elimination of such symptoms, e.g., by a decrease or elimination of symptoms associated with ALS, and/or by a decrease in the duration of such symptoms.