1.Cancer Immunotherapy - The Target is Precisely on The Cancer and Also Not.
Si Lin KOO ; Who Whong WANG ; Han Chong TOH
Annals of the Academy of Medicine, Singapore 2018;47(9):381-387
In recent years, the impressive number of cancer immunotherapy drugs approved has been unprecedented-building on over a century of understanding on how the immune system combats cancer, and how cancer evades it. Leading the charge are the immune checkpoint inhibitor monoclonal antibodies, and adoptive cell therapy with chimeric- antigen-receptor (CAR)-T cell therapy. These breakthrough therapies have led to improved survival in patients with many advanced cancers. Some of the clinical outcomes have been striking, and may even be potentially curative in some terminal cancer patients. While immune checkpoint inhibitors work by blocking regulatory immune checkpoint signals between cancer and the immune cells to awaken an effective anticancer immunity, CAR-T cell therapy targets specific molecules on cancer cells. Tumour antigens as cancer targets take many forms and may not necessarily be proteins related to known functional cellular mechanisms. The convergence of cutting edge omics, bioinformatics, protein synthesis, immunobiology and immunotherapy have led to novel, potentially highly effective cancer targeting against neoantigens, hence reviving the quest for anticancer vaccines. Early clinical trials of neoantigen vaccines have provided proof-of-principle efficacy, especially in melanoma patients. Combinations of immunotherapies through rational design are underway aiming to further improve clinical outcomes. Moving forward, cancer immunotherapy will gain even more momentum from the discovery of more cancer targets-both on the cancer itself and in the tumour microenvironment as well as the identification of biomarkers of treatment resistance and efficacy.
2.Incidence, risk factors and outcomes of malignancies after kidney transplantation in Singapore: a 12-year experience.
Su Hooi TEO ; Kian-Guan LEE ; Gek Hsiang LIM ; Si Xuan KOO ; Maria Erika RAMIREZ ; Khuan Yew CHOW ; Terence KEE
Singapore medical journal 2019;60(5):253-259
INTRODUCTION:
Data on malignancy after kidney transplantation (KTX) is limited in our region, leading to challenges in the care of renal allograft recipients. We aimed to examine the epidemiology, risk factors and outcomes of post-KTX patients.
METHODS:
A retrospective cohort study was conducted of 491 patients who underwent KTX from 1 January 2000 to 31 December 2011. Data linkage analysis was done between our centre and the National Registry of Diseases Office to determine the standardised incidence ratio (SIR), standardised mortality ratio (SMR) and risk factors for malignancy after KTX.
RESULTS:
31 patients (61.3% male) developed malignancy during this period, and their median age at diagnosis was 50 (range 18-65) years. Median time to malignancy diagnosis was 2.6 (range 0.3-7.9) years, with cumulative incidence of 1%, 4% and 10% at one, five and ten years, respectively. The commonest malignancy type was lymphoma, followed by kidney cancer, colorectal cancer and malignancy of the male genital organs. Multivariate analysis identified cyclosporine use as an independent risk factor for malignancy. Compared to the general population, KTX recipients had higher malignancy and mortality rates after malignancy diagnosis (SIR 3.36; SMR 9.45). Survival rates for KTX recipients with malignancy versus those without malignancy were 100%, 93% and 64% versus 97%, 93% and 83% at one, five and ten years, respectively.
CONCLUSION
KTX was associated with higher mortality and incidence of malignancy. Newer immunosuppressive agents and induction therapies were not found to be risk factors for malignancy, possibly due to our relatively small sample size.