Scientific Highlights from American Society of Hematology Meeting

About CAR-T

CAR-T, or chimeric antigen receptor T-cells, is a new form of cancer immunotherapy in which a patient’s own T cells are removed and then engineered to identify and kill malignant multiple myeloma cells. The use of a patient’s own immune cells to fight cancer is proving to be a promising therapeutic approach in the treatment of some lymphomas.

One characteristic of a cancer cell is its ability to evade an attack by a person’s immune system. Immune cells are constantly surveying the body for potential threats, such as a bacteria or virus. Once the immune system detects such a threat, it initiates an attack against it.

One method of stimulating the immune system to detect cancer cells is referred to as chimeric antigen receptor T cell (CAR-T) therapy. Using this type of treatment, researchers take a sample of blood from the patient, and collect certain immune cells called T-cells.

Through laboratory processes, the collected T-cells are reprogrammed to recognize and attack the patient’s cancer cells. Once the T-cells multiply and reach a certain number in the laboratory (usually hundreds of millions to billions), they are re-infused into the patient. The infused T-cells then circulate throughout the body, attacking the patient’s cancer cells.

CTL019 CAR T-cell Therapy-engineers a patient’s own T cells to teach them to recognize and attack myeloma cells. CTL019 is designed to attack myeloma stem cells, a cell type that can give rise to many more myeloma cells. A pilot study reported that this approach was safe and feasible a phase 2 trial evaluating this approach is ongoing.

BCMA CAR T-cell Therapy-teaches T cells to recognize myeloma cells through a protein called B-cell maturation antigen (BCMA). This approach was reported to have promise in treating myeloma in patients who had already failed other therapies. There are several ongoing trials with BCMA as a target.

Antibody-drug conjugate, GSK2857916
GSK2857916 combines an antibody that recognizes myeloma cells by attaching to the protein BCMA and the drug monomethyl auristatin F (MMAF), which kills the cells after they’re recognized. This is the first time this drug has been studied in humans, and the primary purpose of the study was to find a dose that is safe.

Second-generation CD38 antibody, MOR202
Darzalex, a CD38 antibody, has been shown to work well against myeloma. Early-phase investigations into a new antibody, MOR202, have preliminary results suggesting that the drug is effective against myeloma.

References:

  1. Maude S, Pulsipher M, Boyer M, et al. Efficacy and Safety of CTL019 in the First Phase II Multicenter Trial in Pediatric Relapsed/Refractory Acute Lymphoblastic Leukemia: Results of an Interim Analysis. Proceedings from the 2016 annual meeting of the American Society of Hematology. Abstract #2801.
  2. Boldajipour B, Galetto R, Sommer C, et al. Preclinical Evaluation of Allogeneic Anti-BCMA Chimeric Antigen Receptor T Cells with Safety Switch Domains and Lymphodepletion Resistance for the Treatment of Multiple Myeloma. Proceedings from the 2016 annual meeting of the American Society of Hematology. Abstract #381.
  3. Cohen A, Popat R, Trudel S, et al. First in Human Study with GSK2857916, and Antibody Drug Conjugated to Microtubule-Disrupting Agent Directed Against B-Cell Maturation Antigen (BCMA) in Patients with Relapsed/Refractory Multiple Myeloma (MM): Results from Study BMA117159 Part 1 Dose Escalation. Proceedings from the 2016 annual meeting of the American Society of Hematology. Abstract #1148.
  4. Raab M, Chatterjee M, Goldschmidt H, et al. A Phase I/II Study of the CD38 Antibody MOR202 Alone and in Combination with Pomalidomide or Lenalidomide in Patients with Relapsed or Refractory Multiple Myeloma. Proceedings from the 2016 annual meeting of the American Society of Hematology. Abstract #1152.

 

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