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Cancer immunotherapy, also known as immuno-oncology, uses the immune system to treat cancer. Malignant tumors can be detected by natural killer (NK) cells and T-cells of the immune system because they display tumor-specific antigens, also called neoantigens, which result from mutations in the tumor genome and are recognized as non-self. Tumor-associated antigens (TAAs) are proteins more abundant on the surface of cancer cells compared with normal cells and can initiate a T-cell anti-cancer response. TAAs are shared by a subgroup of patients, but neoantigens are unique to individual patient tumors. Tumors acquire certain characteristics that help them evade immune detection, and the tumor micro-environment creates an immunosuppressive network.
To enhance the ability of T-cells and NK cells to kill cancer cells, immune cells are generated with modified T-cell receptors (TCRs) or expressing chimeric antigen receptors (CARs) designed to target various tumor antigens and neoantigens. Either the patient's own cells (autogeneic) or allogeneic cells are used to generate these types of immunotherapies.
Immune checkpoint proteins are involved in controlling immune responses. Cancers can activate immune checkpoint mechanisms resulting in suppression of the immune system’s anti-tumor response. Immune checkpoint inhibitors are a type of immunotherapy that utilizes antibodies to block immune checkpoint proteins.
Tumors are thought to perpetuate their survival by reprogramming the metabolism of the host. Since increased metabolic stress can decrease antitumor T-cell immune response, some cancer immunotherapy strategies aim to normalize metabolic stress.
Abbvie—Using Calibr's switchable CAR-T platform against solid tumors and other cancers
Calibr—modular ‘switchable’ CAR-T cell that uses antibody-based switch molecules, working towards universal CAR-T based treatments for hematological and solid cancers
Allogene Therapeutics—Using UCART19 against CD19-expressing hematological malignancies, acute lymphoblastic leukemia
Amgen—Using engineered autologous cell therapy (eACT™) platform from Kite Pharma
Atara Biotherapeutics—Off-the-shelf, allogeneic T-cell immunotherapy
Bellicum Pharmaceuticals—GoCAR-T cells incorporate an activation switch needing both the target cancer cells and rimiducid
bluebird bio—Partnered with Celgene, developing a CAR-T therapy called bb2121 targeting b-cell maturation antigen (BCMA) for multiple myeloma
CARsgen Therapeutics—anti-Claudin18.2-CAR-T for gastric and pancreatic cancer began a Phase I clinical trial in 2017
Cellectis—creating “off-the-shelf” allogeneic products called universal chimeric antigen receptor T-cells (UCART)
Cell Design Labs—Throttle™, CAR-T cells with small molecule control of an “on/off” switch and synNotch™, a synthetic gene expression system in CAR-T cells for better tumor recognition and specificity
Celularity—CAR constructs for allogeneic CAR-T/NK products
Celyad—CAR-T NK cell-based immunotherapies for cancer
Fate Therapeutics—off-the-shelf CAR T-cell product candidate FT819 derived from iPS Cells
Janssen Biotech—Experimental CART-cell therapy LCAR-B38M for myeloma
Kite Pharma—CAR-T cell therapy called Yescarta U.S. FDA approved for treatment of relapsed or refractory large B-cell lymphoma
Medisix Therapeutics
Mustang Bio—proprietary CAR-T technology and developing CAR-T therapies with CRISPR/Cas9 for hematologic malignancies and solid tumors
Nanjing Legend Biotech
Novartis—U.S. FDA approved CAR-T cell therapy, Kymriah, which uses self-derived cells for treatment of B-cell acute lymphoblastic leukemia
Pfizer—Phase I clinical trials ongoing as of 2018 for allogeneic CAR-T cell therapy UCART19
Precision BioSciences—Collaborating with Baxalta to develop allogeneic CAR-T therapies
Poseida Therapeutics—P-PSMA-101, a PSMA-specific stem cell memory CAR-T drug candidate for prostate cancer
Sorrento Therapeutics—anti-CEA CAR-T in clinical trials with patients with carcinoembryonic antigen–positive (CEA+) cancers
Zencapsule—develops delivery systems for immune checkpoint inhibitors
Ziopharm—non-viral “Sleeping Beauty” (SB) platform for manufacturing of genetically modified CAR+ T cells
Agios Pharmaceuticals —Partnered with Celgene for a metabolic immune-oncology approach that involves altering the metabolic state of immune cells to enhance the immune response to cancer
PD-1 inhibitors include pembrolizumab and nivolumab.
PD-L1 inhibitors include atezolizumab, avelumab, and durvalumab.
