From Vaccines to Cancer Vaccines

Question 1

Different types of Immunotherapy

Answer 1

Peptide vaccines
DC Vaccines
Allogeneic whole cell vaccines
Checkpoint Inhibitors
Oncolytic viruses

Question 2

Passive Immunotherapy

Answer 2

includes the use of tumour specific mAbs, cytokines, adoptive cell transfer

Question 3

Active Immunotherapy

Answer 3

Refers peptide, DC (dendritic cells) or allogeneic whole cell vaccines, vaccines, checkpoint inhibtitors and oncolytic viruses

Question 4

What to consider when designing an antigen specific vaccine

Answer 4

1. Need to choose carefully the antigen, then chose which part of the
   antigen will be used (polypeptides vs long peptide).
2. Choose a delivery system (i.e RNA/DNA vector, Immunobody®,
   Shigella, liposomal cationic adjuvant formulation 09 (CAF09), patient’s
   own DC, etc…)
3. Choose the most appropriate adjuvant (i.e GM-CSF, Poly-IC, CpG,
   IRX…..) to potentiate/direct the immune response.
4. Route of delivery
5. Removing the “brakes” and/or other immuno-suppressive cells.

Question 5

hPAP - Human prostatic acid phosphetase

Answer 5

• A prostate epithelium-specific differentiation
  antigen initially found in seminal fluid.
• First used as a biomarker for prostate cancer (PCa) patients, particularly those with bone
  metastasis and later replaced with more ‘reliable’ PSA

Question 6

Provenge (R) (Sipuleucel-T)

Answer 6

• First and inly FDA approved immunotherapy for advanced prostate cancer.
• Patients who received the vaccine have a 4.1 months increased Median survival
• The treatment consist of co-culturing the patient’s own PBMC with GM-CSF-PAP fused protein for 3 days
  and then re-inject the cells back to the patient, repeated 2 more times 2 weeks apart.
• Patients developed T cell proliferation and interferon-γ responses detectable in the blood following
  treatment*.
• > 3 folds increase in infiltrating CD3(+), CD4(+) FOXP3(-), and CD8(+) T cells observed in the RP tissues
  compared with the pre-treatment biopsy*
• Most infiltrating T cells were PD-1(+) and Ki-67(+)*

Question 7

Mechanism of Cancer Vaccines

Answer 7

• Peptide-based vaccines, nucleic acid-based vaccines need more processing steps after entering the body being presenting to T cells by DCs.
• DNA and RNA vaccines more suited to deliver MHC I presentation antigens than peptide vaccines.
• Tumour antigens are processed by DCS and transported to the cell surface of MHC I and II molecules.
• Interaction between MHC-peptide complex-T cell receptor and cognate receptor-ligand pairs activate T cells.
• Activated CD4+ T cells induce B cells to differentiate into plasma and memory B cells
• Activated T cells differentiated into CD8+ memory T cells and CD8+ effector T cells
• Effector T cells, B cells, antibodies and some cytokines kill tumour cells directly or indirectly.

Question 8

Resistance of Cancer Vaccines

Answer 8

A - Tumour Eternal Resistance: Immunosuppressive cells and immunosuppressive cytokines can inhibit the activation of effector T cells and DC-mediate T cells directly and indirectly in TME.
B - Tumour Intrinsic Resistance: Mutations in signalling pathways, pathways supporting tumour-immune control, loss of tumour antigen expression, changes in antigen processing pathways, loss of HLA expression, epigenetic changes, increased expression of immunosupressive ligands.
C- Immune selection: Immunosurveillance to tumour escape.

Question 9

Cancer Vaccine ( Key differences compared to vaccine against pathogens)

Answer 9

• Given to cure / extend life
• Self-Antigen
• Problem with tolerance and nonimmunogenic
• Main goal is to generate Cytotoxic
  T-cells
• Cancer cells have evolved many
  mechanisms to evade
  immunotherapy

Question 10

Vaccine against pathogens (key differences compared to a cancer vaccine)

Answer 10

• Administrated to prevent disease
• Foreign antigen
• Very immunogenic
• Main goal is to stimulate B-cells to
  produce protective antibodies
• While virus can also evade the
  immune system vaccine can prevent
  their entry into the cells