25.3

Procedure for CAR-T Therapy

CAR T cell therapy is a complex and multistep process in which initially the patients

are evaluated through different tests to determine if CAR-T therapy is an appropriate

treatment option. Subsequently, T cells are collected from the patient’s blood. These

autologous T cells are then genetically engineered to express CARs on their surface.

The engineered T cells are expanded by growing those in the laboratory. When

millions of CAR-transduced T cells are generated, the cells are infused in a process

similar to blood transfusion (Fig. 25.1).

25.4

Targets for CAR-T Therapy

Choosing the right target is critical for the success of any therapy. Cancer being a

heterogeneous disease contributes to the complexity in choosing the right target for

CAR-T therapy. The antigens to be targeted must be expressed specifically on MM

cells to avoid off-target side effects as are associated with most of the

chemotherapeutics. Several tumor antigens are studied and are in clinical trials for

CAR-T therapy for MM including B cell maturation antigen (BCMA), CD19,

CD138, signaling lymphocytic activation molecule 7 (SLAM7), and immunoglobu-

lin light chains.

25.4.1 B Cell Maturation Antigen

B cell maturation antigen (BCMA) is expressed in a subpopulation of B cells, normal

plasma cells, and myeloma cells but not in other hematological cells like

hematopoietic stem cells or normal tissues (Tai and Anderson 2015). BCMA is

also absent on naive and most memory B cells (Xu and Lam 2001). An advantage of

using BCMA as an antigen for CAR-T therapy is reduced off-target toxicity.

However, a major disadvantage is that B cell tumors release/shed soluble BCMA

into the surrounding tissues and blood which can negatively affect the recognition of

BCMA⁺ MM cells by BCMA-specific CAR T cells (Sanchez et al. 2016). Despite

this, the demonstrated involvement of BCMA in MM development makes it the most

popular target for MM CAR-T therapy. In MM, CAR T cells targeting BCMA have

been investigated in a number of studies and have demonstrated important disease-

remitting activity.

25.4.2 CD19

CD19 is a member of immunoglobulin superfamily and acts as a dominant signaling

component on the surface of mature B cells. However, CD19 expression is lost in

plasma cells. CD19 is rarely expressed on MM cells, but studies have revealed the

expression of CD19 on MM stem cell subset. The MM stem cells are a distinct

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E. S. Sinha