Herv-k antibody, cell, vaccine, and drug therapeutics

A method for measuring the increased risk of cancer metastasis in early stages of cancer, comprising the step of:

• measuring the increase of HERV-K expression in early stages of cancer;
• wherein an increase of HERV-K expression in early stages of cancer indicates the increased risk of cancer metastasis.

A human tumor mouse (HTM) model selected from the group consisting of MDA-MB-231 (HTM1) or MDA-MB-468 (HTM2).

TCR sequences generated from tumor infiltrating lymphocytes (TILs) 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 CD8 TCR or CD3 TCR.

A platform for enabling functional matching T cell receptor (TCR) sequences, wherein the platform comprises a small number of homogenous HERV-K specific T cell (K-T cell) populations each obtained from a single clonally expanded K-T cell.

A method for obtaining cells that secrete IFNγ, comprising the step of obtaining HERV-K specific T cells (K-T cells) from tumor infiltrating lymphocytes or peripheral blood mononuclear cells.

A dendritic cell that has been transfected with HERV-K surface (SU) envelope (Env) protein for use as a cancer vaccine.

A peripheral blood mononuclear cell, wherein the cell has been in vitro stimulated with their autologous dendritic cells pulsed with KSU protein (K-T cells).

A combination therapy method of treating cancer, comprising the administration to a subject in need thereof a therapeutically effective amount of:

• (a) a checkpoint inhibitor;
• and
• (b) a HERV-K therapy selected from the group consisting of antibodies, T cell receptors (TCRs), vaccines, peptides, shRNAs, and other drugs.

A method of producing antibodies from mice immunized with 5 multiple antigen peptides (MAPs) that are generated from HERV-K SU protein produced by cancer patients.

The use of HERV-K as a stem cell marker.

A method for the overexpression of HERV-K, comprising the step of:

• administering cancer cells with agents that induce expression of HERV-K by innate immune response (Poly I:C treatment) or LTR hypomethylation (5-Aza), wherein the administration provokes the cancer cells to increase production of a target that makes the cancer cells more susceptible to targeted therapy to include targeted immunotherapy.

A platform to determine the binding kinetics and cell-to-cell interactions of every cell in a microwell slab, comprising:

• (a) polydimethyl siloxane (PDMS) arrays of nanowells, and
• (b) cultured cells from mammospheres obtained from patient breast tumor tissues.

The use of the immunosuppressive domain (ISD) of HERV-K as an immune checkpoint on cancer cells.

A method of regulating chemotherapeutic drug sensitivity, comprising the step of regulating HERV-K activity.

A method of blockading reactive oxygen species signaling, comprising the step of inhibiting HERV-K expression.

A method of decreasing reactive oxygen species-mediated induction of epithelial-mesenchymal transition (EMT), comprising the step of inhibiting HERV-K expression.

The use of the HERV-K env gene to:

• (a) promote expression of an oncogene selected from the group consisting of Ras, p-ERK, c-myc, HIF-1alpha, and AMPK beta;
• or
• (b) downregulate expression of a gene selected form the group consisting of caspase 3, caspase 9, p-RB, CIDEA, p-P38, eNOS, and AMPK alpha.

The use of HERV-K as an upstream modulator of the Ras/ERK signaling pathway.

A method for activating Ras in humans, that does not involve the mutational activation of Ras genes, comprising the step of increasing HERV-K activity.

A method for decreasing Ras activity in humans, comprising the step of decreasing HERV-K expression.

Sequences of HERV-K Envelope (Env), Gag, and Pol genes and RNAs extracted from viral particles isolated from breast cancer patients.