7. Cancer Immunotherapy and Checkpoints

Faridi - 643

List the functions of the immune cells

What are antigen presenting cells (APCs)?

• Professional v Non-professional

• Where are MHC II found

• Where are MHC I found

  • CD4+ v CD8+

After antigens are processed by immature dentritic cells (DCs), what happens?

• CD4+, CD8+

Using the Kaplam-Meier survival analysis, how can we know if a new therapeutic is an improvement in cancer therapy?

What is the MOA of Rituximab? Which molecule does the agent block?

Know B cell lymphomas over express B cells on cell marker, and want to kill those cells

• Rituximab therapy "huge game changer" in patient overall time and survival, brought other monoclonal antibodies to light

List the monoclonal antibodies used for cancer immunology

• Antibody - what is its target and its approved treatment

• Rituximan targets CD20 and is indicated for non-Hodgkin lymphoma

  • B cell lymphoma

• Trastuzumab targets HER2/neu and is indicated for breast cancer, gastric or gastroesophageal junction adenocarcinoma

What is antibody dependent cell mediated cytotoxicity (ADCC)

What is antibody dependent cell mediated phagocytosis (ADCP)?

Signaling lymphocytic activation molecule (SLAM) receptor family

What slide is saying:

• Many of these antibodies, they activate, you know, or they kill the tumor cells in different ways, so they can do it through the cytotoxicity, through the phagocytosis, and then by blocking

• These pathways.

• The cell signaling pathways.

Genentech’s T-DM1 Kadcyla (Ado-Trastuzumab Emtansine)

Cancer immunotherapy - Monoclonal Antibodies

• List the Immune checkpoint inhibitors (ICIs)

  • antibody, its target, and indication

    • Only need to know the ones in red

Immune activation in lymph nodes

• What two signals are needed for this activation?

B7 cell-surface protein ligands

Negative checkpoints in lymph nodes - prevent overactivation

What is the significance of immune checkpoints (breaks → off)

How do cancer cell utilize checkpoint mechanisms

Immune checkpoint inhibitors

Pembrolizuman (Keytruda)

• normal immune response

• tumor evasion and T-cell deactivation

• T-cell reactivation with KEYTUDA

PD1 (anti-programmed cell death protein 1) inhibitors (3)

• all bind to PD-1 and inhibits its interaction with its receptors

PDL1 (anti-programmed death ligand 1) inhibitor (3)

What is the significance of CTLA-4 (cytotoxic T-lymphocyte associated antigen 4) - checkpoint inhibitors

• List the CTLA-4 inhibitors

What is the lymphocyte activation gene 3 (LAG-3)? Which agents blocks LAG-3? What does anti-LAG3 treat?

What are the FDA approved Immune Checkpoint Inhibitors (ICIs)?

• only need to know the highlighted ones

Know the MOA of treating B-cell cancer with T cells expressing anti-CD19 chimeric antigen receptors (CAR)

Chimeric antigen receptor (CAR) T cell (CAR-T) Therapy

MOA of CAR-T Agent - Kymriah (Tisagenlecleucel)

Aucatzyl