Cell-based

Question 1

What cells would you use to fight type I diabetes (autoimmunity), Graft vs host disease and transplant rejection (allogeneic transplantation), HIV (infection) and hematologic and solid cancer respectively?

Answer 1

• Type I diabetes: CAR-Treg, Treg
• Graft vs host disease: CAR-Treg, Treg
• Transplant rejection: CAR-Treg, Treg
• HIV: CAR-T
• Hematologic cancer: CAR-T, CAR-NK, engineered TCR
• Solid cancer: CAR-T, CAR-NK, engineered TCR, TILs

Question 2

What are some types of cell therapies?

Answer 2

• Non-engineered immune cell therapies (Adpotive Cell Therapies), where you use a patient’s immune cells to fight off disease, either Treg isolation and expansion or T cell isolation and expansion.
• There are also dentritic cells and gamma-delta-T cells
• Engineered immune cell therapies where immune cells (engineered TCR, CAR-T, CAAR-T, CAR-Treg and CAR-NK) are isolated, genetically modified and then expansion.

Question 3

What are the main type of APCs (professional Antigen Presenting Cells)?

Answer 3

• Dendritic cells (DCs)
• Macrophages
• B cells

Dendritic cells are the main antigen-presenting cells for B cells. They are the most potent APCs, in cancer they present tumor antigens. T cell responses are initiated by activated DCs.

Question 4

What is antigen processing?

Answer 4

The events that occur within the cell and lead up to the display on the surface.

Question 5

What is antigen presentation?

Answer 5

APC is loaded with the peptide on its surface in a way that the T cell can “see” it.

Question 6

What can DCs do?

Answer 6

They are able to migrate to draining lymph nodes and they are able to transport tumor antigen, which they present to T cells and initiate T cell activation (required for T cell dependent immunity and response to immune checkpoint blockade).

Question 7

What are the functional classes of DCs?

Answer 7

Plasmacytoid DCs (pDCs)
- Express CD123
Conventional DCs (cDCs)
- Express CD11c

Question 8

What does cDC1s do in tumor environment?

Answer 8

• cDC1s interact with various immune cells (e.g. NK, T, macrophages) through cytokines and chemokines.
• cDC1s have the capacity to cross-present exogenous antigen to CD8+ T cells and stimulate naive and previously activated T cells ex vivo.

Question 9

Which are the in vivo activation forms of DCs?

Answer 9

1) Toll like receptor (TLR) agonists: pathogen and damage sensors. Mediating the immune responses towards a wide variety of pathogen-derived ligands and link adaptive immunity with the innate immunity (DC-bridge).
2) STING (Stimulator of interferon genes): induces type 1 IFN production when cells are infected with intracellular pathogens. Type I IFN protects infected cells and nearby cells from local infection nu binding to the same cell that secretes it (autocrine signaling) and nearby cells (paracrine signaling).

Question 10

Which are the in vivo expansion forms of DCs?

Answer 10

1) Expansion and activation of CD103+ DC progenitrors at the tumor site enhances tumor response to therapeutic PD-L1 and BRAF inhibition.
2) Systemic injection of Flt3L leads to systemic expansion of the cDC1 population and restores anti-tumor T cell immunity.
3) Restoring cDC function in advanced PDAC improces efficacy of radiation therapy.