HUMAN ONCOLOGY INVOLVES THE USE OF IMMUNE CHECKPOINT INHIBITION. PROVIDE THREE (3) SPECIFIC EXAMPLES OF FDA-APPROVED HUMAN CHECKPOINT INHIBITORS AND STATE WHICH PATHWAY THEY EACH INHIBIT.

HUMAN ONCOLOGY INVOLVES THE USE OF IMMUNE CHECKPOINT INHIBITION. PROVIDE THREE (3) SPECIFIC EXAMPLES OF FDA-APPROVED HUMAN CHECKPOINT INHIBITORS AND STATE WHICH PATHWAY THEY EACH INHIBIT.

Human oncology involves the use of immune checkpoint inhibition. Provide
three (3) specific examples of FDA-approved human checkpoint inhibitors and
state which pathway they each inhibit.

1. Based on recent advances in human and veterinary oncology, cancer immunotherapy
is now an important consideration in the treatment of some malignancies.
Answer all parts of this question:
a) Human oncology involves the use of immune checkpoint inhibition. Provide
three (3) specific examples of FDA-approved human checkpoint inhibitors and
state which pathway they each inhibit. (3 marks)
b) Briefly define an ‘immune checkpoint’ and list five (5) therapeutic mechanisms
that inhibit immune checkpoint blockade. You may use a diagram to illustrate
your answer. (3.5 marks)
c) List five (5) each, total ten (10), of the expected toxicities of inhibitors for
both of the two (2) major immune checkpoint inhibitor pathways. State which
pathway has more expected side effects. (3.5 marks)
d) Currently, three or more animal health companies have checkpoint inhibitors in
early-stage development for use in veterinary oncology.
Answer both parts of this sub-question:
i. Give three (3) reasons for a veterinary oncologist to not utilise a
commercially available checkpoint inhibitor in a dog, when it is FDAapproved
for use in human patients. (3 marks)
ii. In the context of Fab and Fc, briefly discuss changes that must be made
to the monoclonal antibody in order for it to be potentially effective in
a dog. (2 marks)
Question 1 continued over page
Veterinary Oncology Paper 1 Page 3 of 9
e) Oncept from Merial received United States Department of Agriculture (USDA)
conditional approval in 2007, and then full approval in 2009, for the treatment
of locally controlled stage II/III oral malignant melanoma.
Answer all parts of this sub-question:
i. State the active ingredient of Oncept®. (0.5 marks)
ii. Briefly explain why Oncept must be injected intramuscularly.
(1 mark)
iii. Briefly explain the general mechanism of action for Oncept. (1 mark)
iv. From the list below select the percentage of dogs that make antigenspecific
T-cells following vaccination with Oncept; you must write
your answer in your answer booklet not on this paper: (1 mark)
 approximately 25%,
 approximately 50%,
 approximately 75%,
 or approximately 100%.
v. List three (3) reported side effects from Oncept treatment in dogs.
(1.5 marks)
vi. Subsequent to full USDA-licensure in 2009 there have been a number
of studies that question the efficacy of this product.
Compare and contrast the experimental design and conclusions of the
USDA licensure trial (i.e. Grosenbaugh et al, American Journal of
Veterinary Research 2011) and these more recent negative studies by
providing five (5) aspects to the USDA licensure studies versus
providing five (5) aspects for the more questioning efficacy studies
(i.e. five (5) for each, ten (10) in total). (10 marks)

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