Module 2 - readings Flashcards
(12 cards)
Use of tumor infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma - Rosenberg et al. 1988
Investigating TIL therapy for patients with metastatic melanoma. Treated 20 patients with lymphocytes and IL-2 following immunodepletion.
9/15 patients who had no prior treatment saw regression of cancer. IL-2 with lymphocytes caused increase response than IL-2 alone. Majority had partial responses likely due to immune checkpoints.
Safety and tumour responses with Lambrolizumab (anti-PD-1) in melanoma - Hamid et al. 2013
Investigates the efficacy and safety of lambrolizumab (anti-PD-1 antibody) in patients with advanced melanoma - inhibiting the tumours mechanism to evade immune detection.
Lambrolizumab treatment was more effective than traditional immunotherapies and had lower toxicity 38% of patients responded to treatment with these responders remaining progression free for >7 months.
Patients experienced few grade 3/4 adverse effects with most common events being fatigue, rash and diarrhoea.
Biopsies of regressing tumours exhibited CD8+ T cell infiltration.
Nivolumab and ipilimumab versus ipilimumab in untreated melanoma - Postow et al. 2015
Evaluated the efficacy and safety of combination of nivolumab (anti-PD-1) and ipilumab (anti-CTL-4) vs ipilimumab monotherapy in previously untreated patients with advanced melanoma.
61% of WT BRAF cohort and 52% of MT BRAF responded to combintion therapy - more significant than monotherapy. Responses were durable and lasted long term.
Response was independent of PD-L1 expression. Responses were associated with CD8+ T cell infiltration in tumours
Individualised neoantigen therapy mRNA-4157 plus pembrolizumab versus pembrolizumab monotherapy in restricted melanoma - Weber et al. 2024
Looked at the use of a personalised mRNA neoantigen vaccine in combination with pembrolizumab in patients with resected melanoma.
There was a significant reduction in recurrence or death in the combination group compared to the control group - neoantigen-specific T cells were tectable in blood and tumour tissue. The vaccine was well tolerated with mild to moderate side effects.
Improved survival with ipilimumab in patients with metastatic melanoma - Hodi et al. 2010
Aimed to investigate whether ipilimumab (Anti-CTLA4) is more effective when administered with a gp100 vaccine in metastatic melanoma patients.
Both Ipilimumab groups had improved overall survival when compared to gp100 alone but no significant difference between combination vs monotherapy.
Highest percentage of patients with PFS and response was in the ipilimumab group alone with 60% maintaing response for atleast 2 years > addition of gp100 did not improve efficacy of ipilimumab.
Tumor Regression in Patients With Metastatic Synovial Cell Sarcoma and Melanoma Using Genetically Engineered Lymphocytes Reactive With NY-ESO-1 - Robbines et al. 2011
Investigate the use of engineered TCR adoptive therapy, targeting NY-ESO-1 antigen in both metastatic synovial cell sarcoma and melanoma patients.
Autologous T cells with transduced TCR. 5/11 patients with metastatic melanoma experienced an objective response with 2 complete responses. 4/6 patients with synovial cell sarcoma had partial regression with one having an 18 month long response.
No toxicities were observed in relation to the engineered T cells. T cells remained in blood up to one month post treatment.
Talimogene Laherparepvec Improves Durable Response Rate in Patients With Advanced Melanoma - Andtbacka et al. 2015
Explored the use of oncolytic viral therapy using T-VEC for patients with advanced melanoma. Stimulates an immune response via causing tumour cells to burst and releasing proteins.
T-VEC had a significantly higher response rate (10.8% had complete response) when compared to control group. T-VEC elicited a longer response (>12 months) and improved survival rates.
Treatment was safe and well-tolerated with minimum serious adverse effects.
Oncolytic Virotherapy Promotes Intratumoral T Cell Infiltration and Improves Anti-PD-1 Immunotherapy - Ribas et al. 2017
Investigated whether T-VEC combined with pembrolizumab (anti-PD-1) improves anti-PD-1 immunotherapy.
62% of patients had tumour shrinkage, 22% had complete disappearance of lesions - accompanied by a significant increase in PFS. CD8+ T cell infiltration was enhanced with a increase in NK and B cells too.
Very rarely were there serious events with most side effects being mild mostly well tolerated.
An RNA vaccine drives immunity in checkpoint-inhibitor-treated melanoma - Sahin et al. 2020
Assess the safety and efficacy of the FixVac vaccine (encodes 4 antigens) in melanoma patients who have been treated with an anti-PD-1.
Those that were checkpoint-inhibitor-treated elicited increased immune activation, restored sensitivitiy to CPI. A large portion of patients showed partial responses with durable responses.
Evaluation of the TCR’s extracted from CD8+ T cells of treatment groups showed lysis of melanoma cell lines = shows tumoricidal capacity.
Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma - Nathan et al. 2021
Investigated the use of a bispecific fusion protein tebentafusp in metastatic uveal melanoma > binds GP100 and anti-CD3.
In comparison to current immunotherapies it significantly increased survival after one year and PFS also increased. 99% of patients had AE with a great amount of extreme AE - was not well tolerated.
There was some development of anti-tebentafusp antibodies but this had not apparent impact.
Relatlimab and Nivolumab versus Nivolumab in Untreated Advanced Melanoma - Tawbi et al. 2022
Looked at a combination of CPI relatlimab (anti-LAG-3) and nivolumab (anti-PD-1).
Showed significant improvement in patients which are PD-L1 (-) so didn’t respond well to other immunotherapies. Showed improved outcomes regardless of LAG-3 expression.
More frequent grade 3/4 AE in combination than monotherapy but these were all predictable and manageable with standard care.
CRISPR-engineered T cells in patients withrefractory cancer - Stadtmauer et al. 2020
Using CRISPR in TCR adoptive cell therapy to improve its efficacy for treating refractory cancer patients.
CRISPR used to KO 3 genes in T cells to avoid TCR mismatching, TCR transgene was transduced which specifically targeted NY-ESO-1 and LAGE-1.
Patients received a pre-treatment lymphodepleting chemotherapy creating an optimal environment for T-cell expansion.
T cells persisted in the blood of patients and were successfully targeted to their respective cancer sites.
Evidence for memory T cells = adaptive immune system = sustained protection.
Mixed responses with a single patient showing 50% tumour regression for 4 months , other patients showed little changes. High amount of serious AE experienced but these were due to chemo.
