Cytokine-modified Mycobacterium smegmatis as a novel anticancer immunotherapy

International Journal of Cancer. Journal International Du Cancer
Sarah L YoungAndrew M Jackson

Abstract

Intravesical administration of live M. bovis BCG organisms for carcinoma in situ of the urinary bladder is the most successful immunotherapy for solid malignancy. Nevertheless BCG-therapy is associated with significant toxicity and is ineffective in 30-40% of cases. Recently it has been proposed that cytokine-modified mycobacteria may give greater efficacy. As any immunotherapy involving administration of live BCG organisms (wild-type or recombinant) is likely to have associated toxicity (notably in the immunocompromised), we examined the anti-tumour potential of the closely related nonpathogenic organism, Mycobacterium smegmatis, and a TNFalpha gene-modified recombinant M. smegmatis. When wild-type M. smegmatis were delivered to immunocompetent C57Bl/6 mice bearing the transplantable MB49 bladder tumour, efficacy comparable to live BCG was observed with 10-20% long-term survival. However, this effect was lost in both Nude and Beige mice, lacking functional T and NK cells, respectively. Recombinant M. smegmatis secreting TNFalpha, however, gave a 70% durable tumour-free survival. Lymphocytes from draining lymph-nodes and spleens of these mice exhibited pronounced IFNgamma production to mycobacterial-antigen and tumour-lysate, i...Continue Reading

Citations

Jul 20, 2010·Immunotherapy·Anton B AlexandroffAndrew M Jackson
Dec 1, 2015·Frontiers in Pharmacology·Sumanpreet Kaur, Sukhraj Kaur
Mar 22, 2015·Applied Microbiology and Biotechnology·K R BegniniF K Seixas
Feb 25, 2005·Journal of Leukocyte Biology·José M Martín-FernándezJosé R Regueiro
May 3, 2013·PloS One·Russell S TaichmanKenneth J Pienta
Sep 7, 2018·Experimental and Therapeutic Medicine·Wen JianYing Xue
Jul 17, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sabine KuhnFranca Ronchese
Nov 8, 2008·The Journal of Organic Chemistry·Bert Fraser-ReidChangalvala V S Ramamurty
Jun 5, 2021·Investigative and Clinical Urology·Hyung Suk Kim, Ho Kyung Seo

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Biology: Molecular Imaging

Molecular imaging enables noninvasive imaging of key molecules that are crucial to tumor biology. Discover the latest research in molecular imaging in cancer biology in this feed.

Bladder Carcinoma In Situ

Bladder Carcinoma In Situ is a superficial bladder cancer that occurs on the surface layer of the bladder. Discover the latest research on this precancerous condition in this feed.