Lecture 12 - cancer immunotherapy 2 Flashcards
describe micro-satellite instability and mismatch DNA repair
Microsatellite is a set of short repeated DNA sequences in which certain DNA motifs are repeated, typically 5–50 times
Microsatellite instability result from impaired DNA mismatch repair
MMR corrects DNA errors that spontaneously occur during DNA replication (single base mismatches, short insertion or deletion)
Prevent mutations
Defects in MMR are associated with genome-wide instability
and increased TMB.
what are tumours with high MSI ?
stomach, colorectal and uterine cancers
when is permbrolizumab used in treatment ?
treatment of adult and pediatric patients with unresectable or metastatic solid tumours that have been identified as having a biomarker referred to as microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR).
what are side effects of checkpoints inhibitors?
Diarrhea
Pneumonitis
Rashes and itchiness
Problems with some hormone levels
Kidney infections
what are administration doses of check point inhibitors?
Intravenous infusion every 3 weeks until disease progression or up to 24 month in patients without disease progression
Atezolizumab (PD L1) now available as a subcutaneous injection. Cuts treatment time from 7 minutes from about 30 to 60 minutes for an infusion.
Why does checkpoint inhibitors worked better in some patients
dependant on potential for immunogenicity and presence of T cells. highest chance of response when lots of T cells and high immunogenic
what are CAR T?
chimeric antigen receptors T cell therapy
the T cells are modified to express CARs
CARs are genetically engineered receptors that combine the specific binding domains from a tumour targeting antibody with T cell signalling domains to allow specifically targeted antibody redirected T cell activation.
what is a CAR T cell therapy in children sued?
tisagenlecleucel
Kymriah) for treatment of children and adolescent acute lymphoblastic leukaemia patients
Intense chemotherapy cure 80% of paediatric ALL
Effective treatments have been limited for patients whose cancers return, or relapse, after chemotherapy or a stem-cell transplant.
Long-term follow-up from children with relapsed ALL who had been treated with CAR T show 60% of children were still alive and in remission 5 year after
what are CAR T cell therapies examples?
axicabtagene ciloleucel (Yescarta)
Tisagenlecleucel (Kymriah)
what are side effects of CAR T therapy?
cytosine release syndrome
Cytokine release syndrome occurs when a large number white blood cells are activated and release inflammatory cytokines, which in turn activate more white blood cells.
Lead to systemic hyper-inflammation
Neutropenia
Neurotoxicity
what are vaccine sued for cancer prevention?
HPV - cerviacl, anal, oropharyngeal, vaginal, valvular and pencil cancer
Hepatitis B virus for liver cancer
what is HPV?
HPV is a sexually transmitted virus spread by vaginal, anal and oral sex
There are more than 100 types of HPV, of which at least 13 are cancer-causing
HPV DNA detected in 90-100% of cervical cancer specimens compared to 5-20% in epidemiological control specimens
Human papillomavirus DNA required for development of cervical cancer
what is the mehcnaism of HPV infection?
HPV is primary cause of Cervical intraepithelial neoplasia (CIN)
what are the HPV vaccines offered?
Cervarix®: HPV types 16 and 18
Gardasil®: HPV types 16, 18, 6, and 11
Gardasil-9®:HPV types 16, 18, 31, 33, 45, 52, and 58
Two HPV types (16 and 18) cause 70% of precancerous cervical lesions and cancer
Genital warts caused by HPV types 6 or 11
HPV vaccination reduces the risk of developing cervical cancer
