tumor immunology+ immunotherapy

Question 1

DIAGRAM positive antibody test

Answer 1

gives off BROWN colour to show antibody binding eg to tumour

Question 2

why would breast cancer cause neurological disease

Answer 2

antibodies against tumour enter brain and cause auto-immune neurologic disease

Question 3

evidence that the immune system can control tumours

Answer 3

autopsies have showed ppl who had cancer cells, but no symptoms patients with melanoma/skin cancer were treated and free of disease- they donated organs, but recipient developed tumour, suggesting original patient was IMMUNE to tumour, but recipient wasn’t immunosurpression increases risk of cancer men are twice as likely of DYING from cancer than women, as women have stronger immune response

Question 4

what is immunosurveillance and thus significance

Answer 4

malignant cells controlled by immune system thus immunotherapy enhances immune system

Question 5

cancer immunity cycle

Answer 5

cancer cell release antigens which are detected by APC’s, which go to lymph nodes and activate T cells these T cells go to tumours and infiltrate them (tumour infiltrating lymphocytes)- they recognise cancer cells and kill them this causes cancer cells to release more antigens upon death, so cycle repeats

Question 6

feauture of cancer-immunity cycle and significance

Answer 6

at every stage there are immune activators, and INHIBITORS inhibitors are targeted in immune checkpoint blockade

Question 7

problem with cancer-immunity cycle

Answer 7

immune selection pressure causes cancer cells with advantage eg no MHC molecule= no detection by T cells to grow

Question 8

progression of tumour and response

Answer 8

mutation in DNA leads to cancer cells tumour growth causes inflammation, which recruits innate cells (macrophages/NK/APC’s), which then recruit B/T cells

Question 9

whats required for adaptive immunity to cancer

Answer 9

local inflammation from tumour ie danger signal (to recruit immune cells) expression AND recognition of cancer cell antigens

Question 10

problems with immune surveillance of cancer

Answer 10

takes tumour while to cause local inflammation ie must be big enough tumour and normal antigens often similar

Question 11

T cell response to tumour

Answer 11

often detect tumour-specific antigens INSIDE the cancer cell

Question 12

what are tumour specific antigens and example

Answer 12

antigens found only in tumour, not in normal cells tumour cells often have viral antigens eg EBV/HPV, or mutate cellular proteins eg fusion proteins

Question 13

cancers of viral origin according to different kinds of people

Answer 13

cancers that occur mainly in immunosurpressed people are Kaposi sarcoma (HIV) and EBV lymphoma cancers in healthy ppl include HepB/C and HPV genital tumours

Question 14

how HPV causes cancer

Answer 14

due to E6/7 oncoproteins of HPV (intracellular), which causes cervical cancer

Question 15

main treatment against HPV

Answer 15

Gardasil 9 (vaccine), which has just proteins eg E6/7, NOT DNA

Question 16

what are tumour-associate antigens and thus importance for our response

Answer 16

NORMAL cell proteins, but expressed at wrong place/time thus tolerance may need to be overcome (ie normally self reactive lymphocytes deleted, but they may be needed to attack these normal proteins)

Question 17

types of tumour-associated antigens

Answer 17

cancer-testes antigens MAGE family (melanoma-associated antigens) HER2 (breast cancer0 prostate antigens eg PSA

Question 18

what is central tolerance+ location

Answer 18

in thymus, those that are self reactive are deleted, and rest are self tolerant

Question 19

problems with immunotherapy against tumour associated antigens with example

Answer 19

we already have tolerance to auto-antigens even if we can exploit this, leads to autoimmunity as well- in melanoma, leads to vitiligo (depigmentation)

Question 20

types of immunotherapies

Answer 20

antibody therapy therapeutic vaccination immune checkpoint blockade adoptive transfer of immune cells

Question 21

types of monoclonal antibody-based therapy

Answer 21

naked ie just antibody: anti HER2, anti EGFR (colon cancer) conjugated- either to radioactive particle (emits radiation), or to cytotoxic drug (eg anti-HER2) bispecific antibodies- specific to 2 antigens

Question 22

main type of therapeutic cancer vaccination and mechanism, what type of cancer

Answer 22

Provenge- for advanced prostate cancer WBC extracted and fusion protein put in- then put back into body

Question 23

personalised tumour-specific cancer vaccines

Answer 23

DNA extracted from tumour and healthy cells, and compared using genome sequencing- HLA typing also occurs, thus mutation identified, and peptide produced

Question 24

immune checkpoint blockage+ mechanism

Answer 24

rather than stimulate responses, regulatory response inhibited antibodies produced against regulatory T cells

Question 25

adoptive transfer of cells

Answer 25

T cells extracted from blood, may be genetically engineered, and expanded in cultures, and re-infused

Question 26

example: CAR T cell therapy (chimaeric antigen receptor)

Answer 26

T cell extracted, genetically engineered with an antibody fragment (scFv), which binds to antigen of tumour cell, and activates the T cells once infused type of adoptive transfer of cells