This section offers answers to the most common questions about CAR T-cell Therapy.
What’s are Chimeric Antigen Receptors or CARs?
Chimeric antigen receptors or CARs, are recombinant receptor constructs composed of an extracellular single-chain variable fragment (scFv) derived from an antibody which are joined to a hinge/spacer peptide and a transmembrane domain and further linked to the intracellular T-cell signaling domains of the T-cell receptor.
CAR T-cells combine the specificity of an antibody with the cytotoxic and memory functions of T cells
What’s is CAR T-Cell Therapy?
CAR T-cell therapy is a new type of cancer therapy that uses a patient’s own modified white blood cells to kill cancer.
Adoptive transfer of T cells expressing chimeric antigen receptors or CARs is a promising immunotherapy based anti-cancer therapy. CAR-modified T-cells can be engineered to target virtually any tumor associated antigen.
CAR T-Cell Therapy uses T-cells engineered with chimeric antigen receptors for cancer therapy. The premise of CAR-T immunotherapy is to modify T-cells to recognize cancer cells in order to more effectively target and destroy them.
How does CAR T-Cell Therapy work?
The CAR T-cell therapy begins by collecting blood from the patient with cancer. During this process, T -cells are separated and removed from the blood and, depending on the patient’s condition, the remaining blood is returned to the body.
In the next step, called leukapheresis or apheresis, white blood cells are separated from blood. T-cells, which are a type of white blood cells, are genetically altered and the resulting CAR T-cells are re-infuse into the patients.
Before the CAR T-cells are re-infused, the patient receives a brief course of chemotherapy, which improves the chance that the new CAR T-cells will be accepted and not attacked by the immune system when returned to the body.
CAR T-cells can be either derived from T cells in a patient’s own blood (autologous) or derived from the T-cells of another, healthy, donor (allogenic). Once isolated, T-cells are genetically engineered to express a specific CAR, which programs them to target an antigen that is present on the surface of tumors.
For safety, CAR-T cells are engineered to be specific to an antigen expressed on a tumor that is not expressed on healthy cells.
The process of manufacturing CAR T-Cells involves a number of specific steps:
- T-cells are removed from the patient’s own blood.
- Then in a laboratory setting the gene that encodes for the specific antigen receptors are incorporated into the T-cells.
- Thus producing the CAR receptors (labeled as c) on the surface of the cells.
- The newly modified T-cells are then further harvested and grown in the lab.
- After a certain time period, the engineered T-cells are infused back into the patient.
After CAR T-cells are re-infused into a patient, they act as a “living drug” against cancer cells. When they come in contact with their targeted antigen on a cell, CAR T-cells bind to it and become activated, then proceed to proliferate and become cytotoxic.
CAR-T cells destroy cells through several mechanisms, including extensive stimulated cell proliferation, increasing the degree to which they are toxic to other living cells (cytotoxicity), and by causing the increased secretion of factors that can affect other cells such as cytokines, interleukins, and growth factors.
How long does the patient remain in the hospital after receiving CAR T-cell therapy?
Typically, patients need to stay one to one and one-half weeks in the hospital after receiving CAR T-cell therapy. Generally, the length of stay depends on a number of factors, including the patient’s response to treatment and the risk for side effects.
Is CAR T-Cell Therapy Approved in the United States?
Today, 3 CAR T-cell therapies have been approved by the United States Food and Drug Administration (FDA).
- Tisagenlecleucel (Kymriah™; Novartis), was approved for:
- Adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL)
- Young adult patients up to age 25 with relapsed or refractory acute lymphoblastic leukemia (ALL)
- Axicabtagene ciloleucel (Yescarta™; Kite Pharma/Gilead) the first FDA-approved CAR T-cell therapy for adult patients with certain types of advanced B-cell lymphoma.
- Brexucabtagene autoleucel (Tecartus™; Kite Pharma/Gilead) is a FDA-approved CAR T-cell therapy for patients with relapsed or refractory mantle cell lymphoma (MCL).
What’s the success rate of CAR T-cell therapy for lymphoma?
In clinical trials, over 80% of children and young adults treated with Tisagenlecleucel in clinical trials had their cancer go into remission.
An analysis of data from the ELIANA trial (NCT02435849) shows impressive results in 75 patients treated with Tisagenlecleucel. The analysis found the overall remission rate within 3 months was 81%. The trial results also showed event-free survival of 73% at 6 months and 50% at 12 months. Overall Survival (OS) was 90% and 76% over the same time intervals. 
Over 80% of patients who were treated with Axicabtagene ciloleucel experienced either a Complete Response (CR) or Partial Response (PR).
Furthermore, two-year follow-up data from ZUMA-1 trial (NCT02348216) suggest that axicabtagene ciloleucel can induce durable responses and a median overall survival of greater than 2 years, and has a manageable long-term safety profile in patients with relapsed or refractory large B-cell lymphoma. 
Data about the long-term success of both therapies continues to be collected.
Approval of brexucabtagene autoleucel was based on ZUMA-2 (NCT02601313), an open-label, multicenter, single-arm trial of 74 patients with relapsed or refractory MCL who had previously received anthracycline- or bendamustine-containing chemotherapy, an anti-CD20 antibody, and a Bruton tyrosine kinase inhibitor. Patients received a single infusion of brexucabtagene autoleucel following completion of lymphodepleting chemotherapy.
The primary efficacy outcome measure was objective response rate (ORR) per Lugano  criteria as assessed by an independent review committee.
Of the 60 patients evaluable for efficacy based on a minimum duration of follow-up for response of six months, the ORR was 87% (95% CI: 75, 94), with a complete remission (CR) rate of 62% (95% CI: 48, 74). The estimated median duration of response was not reached (range of 0+ to 29.2+ months) after a median follow-up time for duration of response of 8.6 months. Of all 74 leukapheresed patients, the ORR as assessed by independent review committee (IRC) was 80% (95% CI: 69, 88) with a CR rate of 55% (95% CI: 43, 67).
What are some of the Side Effects of CAR T-Cell Therapy
The most common side effects observed with CAR T-cell Therapy are:
- Cytokine release syndrome or CRS, which is similar to flu-like symptoms (headache; fever; chills; severe nausea, vomiting, diarrhea; severe muscle or joint pain), shortness of breath, low blood pressure and fast heart rate. These symptoms are mild in most patients but can be serious and life-threatening.
- Transient neurologic toxicity, can also be experienced and can be serious in some patients. Neurologic events include encephalopathy (brain disease, injury, malfunction), confusion, aphasia (difficulty understand or speaking), drowsiness, agitation, seizures, loss of balance and altered consciousness.
- Neutropenia – an abnormally low number of neutrophil granulocytes, a type of white blood cell, in the blood.
- Febrile neutropenia (the development of fever, often with other signs of infection, in a patient with neutropenia)
- Cytopenias (not resolved within 28 days)
- Anemia – low red blood cell count.
Highlights of prescribing information
Tisagenlecleucel (Kymriah™; Novartis) [Prescribing Information]
Axicabtagene ciloleucel (Yescarta™; Kite Pharma/Gilead) [Prescribing Information]
Brexucabtagene autoleucel (Tecartus™; Kite Pharma/Gilead) [Prescribing Information]
 Determine Efficacy and Safety of CTL019 in Pediatric Patients With Relapsed and Refractory B-cell ALL (ELIANA) – Clinical Trial: NCT02435849
 Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bittencourt H, Bader P, et al. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N Engl J Med 378:439-448, 2018. [Pubmed][Article]
 Safety and Efficacy of KTE-C19 in Adults With Refractory Aggressive Non-Hodgkin Lymphoma (ZUMA-1) – Clinical Trial: NCT02348216
 Locke FL, Ghobadi A, Jacobson CA, Miklos DB, Lekakis LJ, Oluwole OO, Lin Y, et al. Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1-2 trial. Lancet Oncol. 2018 Nov 30. pii: S1470-2045(18)30864-7. doi: 10.1016/S1470-2045(18)30864-7. [PubMed][Article]
 Study to Evaluate the Efficacy of Brexucabtagene Autoleucel (KTE-X19) in Participants With Relapsed/Refractory Mantle Cell Lymphoma (ZUMA-2) – Clinical Trial: NCT02601313
This page was last updated on October 20, 2020