OCC Targeted Therapy & Immunotherapy in Oncology 2 — Questions and Answers
Question 1: Which immune checkpoint molecule does pembrolizumab (Keytruda) target?
- CTLA-4
- PD-1 (Correct answer)
- PD-L1
- LAG-3
Correct answer: PD-1
Pembrolizumab is a humanized monoclonal antibody that targets PD-1 on T cells, blocking the PD-1/PD-L1 interaction and restoring anti-tumor T cell activity.
Question 2: Ipilimumab was the first FDA-approved immune checkpoint inhibitor (2011) and targets which molecule?
- PD-1 on T cells
- PD-L1 on tumor cells
- CTLA-4 on T cells (Correct answer)
- CD28 on T cells
Correct answer: CTLA-4 on T cells
Ipilimumab targets CTLA-4, a negative regulator of T cell activation in lymph nodes, thereby amplifying anti-tumor immune responses in melanoma.
Question 3: What is the first procedural step in manufacturing autologous CAR-T cell therapy for a patient?
- Administer high-dose lymphodepleting chemotherapy
- Perform leukapheresis to collect the patient's T cells (Correct answer)
- Administer G-CSF to mobilize stem cells
- Perform a bone marrow biopsy to assess disease burden
Correct answer: Perform leukapheresis to collect the patient's T cells
Leukapheresis to collect the patient's own T cells is the first manufacturing step; these cells are then genetically engineered to express the chimeric antigen receptor.
Question 4: Which biomarker is most commonly used to predict response to PD-1/PD-L1 checkpoint inhibitors across multiple tumor types?
- HER2 gene amplification
- BCR-ABL fusion transcript
- PD-L1 expression by immunohistochemistry (tumor proportion score) (Correct answer)
- KRAS mutation status
Correct answer: PD-L1 expression by immunohistochemistry (tumor proportion score)
PD-L1 expression measured by IHC is an established predictive biomarker for checkpoint inhibitor response, with higher expression generally correlating with greater benefit.
Question 5: Atezolizumab differs from pembrolizumab and nivolumab in that it targets which molecule?
- PD-1 on T cells
- CTLA-4 on T cells
- PD-L1 on tumor and immune cells (Correct answer)
- LAG-3 on T cells
Correct answer: PD-L1 on tumor and immune cells
Atezolizumab targets PD-L1 (the ligand) rather than PD-1 (the receptor), blocking the interaction from the antigen-presenting or tumor cell side.
Question 6: Blinatumomab is a bispecific T-cell engager (BiTE) that simultaneously binds CD19 on B cells and which molecule on T cells?
- PD-1
- CD3 (Correct answer)
- CD28
- CTLA-4
Correct answer: CD3
Blinatumomab bridges CD19-expressing malignant B cells and CD3-expressing T cells, forcing T cells to recognize and destroy the B cell tumor targets.
Question 7: Microsatellite instability-high (MSI-H) status predicts response to PD-1 inhibitors. Which enzyme deficiency causes MSI-H tumors?
- Topoisomerase II deficiency
- Mismatch repair (MMR) protein deficiency (Correct answer)
- Thymidylate synthase deficiency
- BRCA1/2 deficiency
Correct answer: Mismatch repair (MMR) protein deficiency
MSI-H tumors arise from deficient mismatch repair (dMMR), leading to accumulation of mutations that generate neoantigens, making them highly responsive to PD-1 blockade.
OCC Targeted Therapy & Immunotherapy in Oncology 2
Which immune checkpoint molecule does pembrolizumab (Keytruda) target?