You are here

cancer gentics project 3 excerpt 6

Submitted by jdantonio on Thu, 05/04/2017 - 20:33

Prior to the infusion of our selected and modified T-cell lines we will perform a  myeloablation, the destruction of immune cells in the body by high dose full body radiation treatment and the infusion of hematopoietic stem cells (Wrzesinski et al 2010). This pre treatment of patients has been shown to greatly improve the efficacy of ACT treatments in vivo(Perica et al 2015).  This works by reducing the presence of suppressing regulatory lymphocytes that inhibit cytotoxic T-cell activity(Wrzesinski et al 2010). We would infuse both our adaptive cell lines and our chimeric cell lines at the same time following the myeloablation and would concurrently administer IL-2 by and IV (Kochenderfer et al 2012). After the administration of the treatment we would monitor the patient and be on alert for cytokine toxicity a potential side effect of T-cell adaptive therapies caused by T-cell stimulated release of inflammatory cytokines. This can lead to fever and inflammation in the patient and can in very severe cases cause patient death (Barrett et al 2013). For dosage of the treatment, T-cell numbers are a limiting factor in the treatment. So we would infuse all the T-cells we are able to generate in a reasonable amount of time (maybe a month or two of growth), this amount would vary depending on multiple factors.

 

Barrett DM, Singh N, Porter DL, Grupp SA, and June CH. 2013. Chimeric Antigen Receptor

Therapy for Cancer. Annual Review 65: 333-347.

<http://annualreviews.org/doi/full/10.1146/annurev-med-060512-150254>. Accessed

2017 May 1.



Kochenderfer JN, Dudley ME, Feldman SA,Wilson HW, Spaner DE, Maric I, Stetler-Stevenson

M, Phan GQ, Hughes MS, Sherry MR, Yang JC, Kammula US, Devillier L, Carpenter R,

Nathan DAN, Morgan RA, Laurencot C,and Rosenberg SA. 2012. B-cell depletion and

remissions of malignancy along with cytokine-associated toxicity in a clinical trial of

anti-CD19 chimeric-antigen-receptor-transduced T cells. Blood 119(12):2709-20.

<http://www.bloodjournal.org/content/bloodjournal/119/12/2709.full.pdf>. Accessed

2017 May 1.

 

Perica K, Varela JC, Oelke M, and Schneck J. 2015. Adoptive T Cell Immunotherapy for Cancer.

Rambam Medical Journal 6(1): e0004. National Center of Biotechnology

Information[NCBI]. <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4327320/>.

Accessed 2017 April 29.

 

Wrzesinski C, Paulos CM, Kaiser A, Muranski P, Palmer DC, Gattinoni L, Yu Z, Rosenberg SA,

and Restifo NP. 2010. Increased intensity lymphodepletion enhances tumor treatment

efficacy of adoptively transferred tumor-specific T cells. Journal of Immunotherapy

33(1): 1-7. National Center of Biotechnology Information[NCBI].

Post: