Different Modes of Tumor Immunotherapy - correct answer 1. Passive immunotherapy with monoclonal antibodies or antibody-like molecules
2. Adoptive
... [Show More] cellular therapy with antitumor T cells
3. Immune checkpoint blockade-targeting T cell inhibitory pathways
4. Vaccination with tumor antigens
5. Various other approaches for stimulating antitumor immunity
Passive immunotherapy with Abs or antibody-like molecules - correct answer - Passive antibody therapy: rapid, very specific, without long-lived immunity
- Some anticancer mAbs have been used for>20 years, and many more are now approved or in advanced development
- Recombinant single polypeptide proteins with AB-like Ag-binding sites, termed single chain variable fragments, specific for tumor antigens have been developed for cancer treatment
Adoptive Cellular Therapy with Antitumor T cells - correct answer - This therapy is to transfer of immune cells that have antitumor reactivity into a tumor-bearing host. The immune cells are derived from a cancer patient's blood or solid tumor and then are treated in various ways in vitro to expand their numbers and enhance their antitumor activity, before reinfusion back into the patient
Adoptive Cellular Therapy with Antitumor T cells 2.1 - correct answer - T cells specific for tumor antigens can be harvested from a patient's tumor tissue or blood, expanded and activated in vitro, and infused back into the cancer patients. This approach has some succuss in treating melanoma
- In-vitro: Stimulation of cells with tumor neoantigens and with anti-CD3, anti-CD28 and IL-2
- In-vitro: Transduction of patient's T cells to express TCRs specific for tumor Ag known to be displayed by HLA molecule - using lentiviral expression vector
Chimeric Antigen Receptor T cells Therapy (CAR T cell Therapy) - correct answer - Adoptive therapy using T cells expressing chimeric antigen receptors (CARs) has proved successful in some hematologic malignancies, and it is being developed for other tumors
- CARs are genetically engineered membrane-bound receptors with tumor antigen-specific binding sites encoded by recombinant Ig variable genes (i.e., single chain variable fragments) and cytoplasmic tails containing signaling domains of both the TCR complex and T cell costimulatory receptors
Chimeric Antigen Receptor (CAR) - correct answer - CAR is composed of an extracellular immunoglobulin single chain variable fragment specific for a tumor antigen, and cytoplasmic signaling domains that activate T cells, such as the {} chain immunoreceptor tyrosine-based activation motif (ITAMs) and motifs in the cytoplasmic tails of the costimulatory receptors CD28 and 4-1BB, which promote robust T cell activation
The CAR T Protocol - correct answer - Isolate T cells from peripheral blood of the cancer patient
- Infect with CAR-encoding retroviral or lentiviral vectors
- Stimulate with anti-CD3 and/or anti-CD28 antibodies to expand their numbers
- Transfer (infuse) the expanded CAR-expressing T cells back into patient. (Prior to transfer, the patients are usually treated with drugs that deplete their own lymphocytes, which maximizes the proliferation of transferred CAR-T cells)
- The transferred T cells undergo robust expansion and activation in the patient, in response to tumor antigen recognition by the Ig domain of the CAR and costimulatory signal provided by the signaling domains
- CAR T cell-mediated tumor cell killing: Direct cytotoxicity; Cytokine-mediated mechanisms
CAR T cell Therapy - correct answer - CD19-specific CAR-T cells: For treatment of various B cell malignancies that are refractory to other treatments, including chronic lymphocytic leukemia, acute lymphoblastic leukemia, and B cell lymphomas
- CD20-specific CAR-T cells: For B cell lymphomas
- Memory CAR-T cells may persist in the treated patient, and the immune surveillance against tumor recurrence is maintained
CAR T cell Therapy Unwanted/Adverse Effects - correct answer - CARs specific for CD19: Also kill normal B cells, but not Ab-producing plasma cells (the latter cells do not express CD19) [Show Less]