Cancer immunotherapy

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

Autolus Limited

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

Carina Biotech

CARsgen Therapeutics—anti-Claudin18.2-CAR-T for gastric and pancreatic cancer began a Phase I clinical trial in 2017

Celgene

Cellectis—creating “off-the-shelf” allogeneic products called universal chimeric antigen receptor T-cells (UCART)

Cell Medica

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

Fortress Bio

Gilead Sciences

Janssen Biotech—Experimental CART-cell therapy LCAR-B38M for myeloma

Juno Therapeutics

JW Therapeutics

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

Shire

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.