Lecture 9- immunotherapy Flashcards
what is variolation?
protection from smallpox by inoculation with scab material. Known in China, Middle East and NW Africa since Middle Ages
what is an oriental sore?
Deliberate exposure to sandflies infected with Leishmania to ensure protection from facial scarring
what are the approaches to cancer?
-Surgery – mostly primary cancers
-Chemo / radiotherapy kills fast-growing cells, therefore damaging IR
-Reharnessing immune response vital
what are the approaches to immunotherapy?
Non-specific therapies and cell based therapies –> Immune targeting of disease <– Vaccination strategies and Antibody therapies
how do we prevent cancer?
Gardasil / Carvarix licenced for cervical cancer prophylaxis (Quad vaccine to HPV 6/11/16/18, 9-valent also covers 31/33/45/52/58)
HPV16 / 18 cause 70% of cervical and 75% of anal cancers. HPV 6 / 11 in 90% of genital warts
Shows high level of protection against infection and subsequent disease (up to 87% protection against CIN)
what are CAR-T cells?
Genetic modification of patient’s T cells (autologous)
No GvHD, but risk of off-tumour toxicity and CRS
Clinical trial versions (2nd gen) lag far behind developmental versions of CAR (5th+ generation)
what are the challenges of CAR-T?
Kymriah and 5 other CAR-T therapies now licensed in US and UK for treating B cell acute leukaemia (<25yo) and DLBCL with relapsed / refractory disease
Manufacturing of the therapy is done in the US, though initial processing is done in local centres (including SNBTS in Edinburgh)
Logistically difficult, and issue with ‘economic toxicity’ (cost £282,000 - single dose)
what is the future for immunotherapies?
Immunotherapy covers many aspects of immune stimulation or component usage.
Monoclonal antibodies have been major area of therapeutics for last 20 years.
Cell therapies another major target, allowing replacement of faulty immune system (autoimmune reset) with HSCT
Cell therapies more complex to regulate, but adoptive T cell therapies, CAR-T cells and DC offer improved survival for many diseases.
Combination with other therapeutic approaches essential
what are virus specific T cells?
EBV-driven B cell lymphoma in transplant patients
Very high mortality rate due to poor treatment options
SNBTS T cell bank used to treat over 60 patients with survival rate of 59%
what is BM / HSC transplantation?
First cell therapy for treating blood disorders (BM failure / SCID), and for leukaemia treatment
what is the cytokine cascade in the RA?
Blockade of the RA cytokine cascade by antibodies or receptor mimics controls disease
TNF is the ‘master regulator’ of RA, and key target for Mab therapy.
What are monoclonal antibodies for therapy?
Over 400 monoclonal antibodies in development / clinical trial / therapeutic use – more than 60% for cancer
what re the percentages of stem cell use?
60% = own stem cells
19% = stem cells from an unrelated donor
21% = stem cells from a related donor
