The present disclosure provides methods for genetically modifying lymphocytes and methods for performing adoptive cellular therapy that include transducing T cells and/or NK cells. The methods can include inhibitory RNA molecule(s) and/or engineered signaling polypeptides that can include a lymphoproliferative element, and/or a chimeric antigen receptor (CAR), for example a microenvironment restricted biologic CAR (MRB-CAR). Additional elements of such engineered signaling polypeptides are provided herein, such as those that drive proliferation and regulatory elements therefor, as well as replication incompetent recombinant retroviral particles and packaging cell lines and methods of making the same. Numerous elements and methods for regulating transduced and/or genetically modified T cells and/or NK cells are provided, such as, for example, those including riboswitches, MRB-CARs, recognition domains, and/or pH-modulating agents.

The present invention provides polypeptides for selectively inducing target antigen-specific CD8-positive T-cell responses. Since induction of human immunodeficiency virus (HIV)-specific CD4-positive T-cell responses by vaccine could promote HIV infection, an HIV vaccine antigen that selectively induces HIV-specific CD8-positive T-cell responses would be useful if obtained. Thus, in the present invention, polypeptide antigens were designed in which 8- to 12-residue amino acid sequences divided from the amino acid sequence of a target antigen protein were connected in an order different from that of the original amino acid sequence. DNA and viral vector vaccines expressing these antigens were tested by inoculation into monkeys. As a result, they were shown to be able to efficiently induce antigen-specific CD8-positive T-cell responses in a selective manner. The instant antigens may be useful as vaccine antigens that induce CD8-positive T cells in a highly selective manner.

The present invention provides polypeptides for selectively inducing target antigen-specific CD8-positive T-cell responses. Since induction of human immunodeficiency virus (HIV)-specific CD4-positive T-cell responses by vaccine could promote HIV infection, an HIV vaccine antigen that selectively induces HIV-specific CD8-positive T-cell responses would be useful if obtained. Thus, in the present invention, polypeptide antigens were designed in which 8- to 12-residue amino acid sequences divided from the amino acid sequence of a target antigen protein were connected in an order different from that of the original amino acid sequence. DNA and viral vector vaccines expressing these antigens were tested by inoculation into monkeys. As a result, they were shown to be able to efficiently induce antigen-specific CD8-positive T-cell responses in a selective manner. The instant antigens may be useful as vaccine antigens that induce CD8-positive T cells in a highly selective manner.

The present invention relates to a peptide, or derivative thereof, having length equal to or lower than (30) amino acids, and comprising any one of SEQ ID Nos. 2, 3, 9, 10, 13, 14, 15, 16, 17, 18, or a conservative variant thereof, for use as a medicament, preferably for use in the treatment of conditions associated to/caused by deficient angiogenesis or conditions beneficing from increased angiogenesis.

An analysis of human CD4.sup.+ T-cell epitopes of RV capsid proteins with cross-reactive potential was performed, peptide epitopes of RV-A16 capsid proteins VP1 and VP2 were identified, RV-specific CD4.sup.+ T cells were phenotyped for surface markers and cytokine profiles using flow cytometry, and it was found that, among non-infected subjects, circulating RV-A16-specific CD4.sup.+ T cells detected at the highest frequencies targeted 10 unique epitopes with diverse HLA-DR binding capacity. T-cell epitopes localized to conserved regions of significance to the virus and were enriched for HLA class I and II binding motifs and were activated in vivo after experimental infection with RV-A16. RV-A16 epitopes constituted species-specific and pan-species varieties, together providing 90% coverage of the US population. Cross-reactivity was evidenced for RV-A16 and RV-A39. High-frequency circulating RV-specific memory Th1 cells in healthy individuals preferentially target a limited set of conserved epitopes and these epitopes, separately or combined, can serve as vaccines.

In certain aspects the invention provides immunogenic compositions comprising CH848 HIV-1 envelopes and their use in methods to induce immune responses in subjects, e.g., human subjects.

In certain aspects the invention provides immunogenic compositions comprising CH848 HIV-1 envelopes and their use in methods to induce immune responses in subjects, e.g., human subjects.

Provided herein are lipid particles, such as lentiviral particles, that incorporate or are pseudotyped with a truncated Baboon Endogenous Retrovirus (BaEV) envelope glycoprotein that contains a cytoplasmic tail with a partial inhibitory R peptide that is less than the full length wildtype BaEV inhibitory R peptide. Also provided herein are polynucleotides encoding the truncated BaEV envelope glycoproteins and producer cells for preparation of the lipid particles, such as lentiviral particles, containing the truncated BaEV envelope glycoproteins, as well as methods for preparing and using the lipid particles, such as lentiviral particles.

Provided herein are lipid particles, such as lentiviral particles, that incorporate or are pseudotyped with a truncated Baboon Endogenous Retrovirus (BaEV) envelope glycoprotein that contains a cytoplasmic tail with a partial inhibitory R peptide that is less than the full length wildtype BaEV inhibitory R peptide. Also provided herein are polynucleotides encoding the truncated BaEV envelope glycoproteins and producer cells for preparation of the lipid particles, such as lentiviral particles, containing the truncated BaEV envelope glycoproteins, as well as methods for preparing and using the lipid particles, such as lentiviral particles.

The invention is directed to a system comprising a lentivirus vector particle which encodes at least one guide RNA sequence that is complementary to a first DNA sequence in a host cell genome, a Cas9 protein, and optionally a donor nucleic acid molecule comprising a second DNA sequence. The invention also is directed to a method of altering a DNA sequence in a host cell using such a system, where the host cell can be in a human and the altered DNA can be of the human -globin gene. The invention also is directed to a fusion protein comprising a Cas9 protein and a cyclophilin A (CypA) protein. The invention also is directed to sequences of vectors that can be used in the system and method.