2017
DOI: 10.1016/j.omto.2016.12.004
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Oncolytic Adenoviruses Armed with Tumor Necrosis Factor Alpha and Interleukin-2 Enable Successful Adoptive Cell Therapy

Abstract: Adoptive cell therapy holds much promise in the treatment of cancer but results in solid tumors have been modest. The notable exception is tumor-infiltrating lymphocyte (TIL) therapy of melanoma, but this approach only works with high-dose preconditioning chemotherapy and systemic interleukin (IL)-2 postconditioning, both of which are associated with toxicities. To improve and broaden the applicability of adoptive cell transfer, we constructed oncolytic adenoviruses coding for human IL-2 (hIL2), tumor necrosis… Show more

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Cited by 97 publications
(161 citation statements)
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“…This could invigorate TIL activity in the context of ACT, as shown in melanoma and pancreatic cancer. 20 This is further supported by efficacy data from patient cohorts, where patients with OVCA appeared to benefit from oncolytic adenovirus therapy. 21 Importantly, among a panel of FDA-approved cytokines, TNFa and IL-2 was the combination of cytokines that best synergized with antitumor T cells in our preclinical studies.…”
Section: Open Accessmentioning
confidence: 79%
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“…This could invigorate TIL activity in the context of ACT, as shown in melanoma and pancreatic cancer. 20 This is further supported by efficacy data from patient cohorts, where patients with OVCA appeared to benefit from oncolytic adenovirus therapy. 21 Importantly, among a panel of FDA-approved cytokines, TNFa and IL-2 was the combination of cytokines that best synergized with antitumor T cells in our preclinical studies.…”
Section: Open Accessmentioning
confidence: 79%
“…21 Importantly, among a panel of FDA-approved cytokines, TNFa and IL-2 was the combination of cytokines that best synergized with antitumor T cells in our preclinical studies. 22 23 This translated into promising safety, efficacy and survival results in animals bearing melanoma and pancreatic tumors, following adoptive transfer of TILs, 20 T-cell receptor-engineered T cells 22 and chimeric antigen receptor T cells. 24 Such outcome is attributed to a decrease in intratumororal immunosuppression and, improved trafficking and activation of transferred T cells.…”
Section: Open Accessmentioning
confidence: 99%
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“…The cell death after electrotransfer of pDNA using the EP1 pulse protocol could be a consequence of the production of IFNβ and TNFα. TNFα has shown an antitumor effect on tumor cells or tumors in combination with other treatments [84][85][86][87][88]. Cell lines that possess receptors for INFβ and/ or TNFα and receptor binding can activate necroptosis or apoptosis [89,90].…”
Section: Discussionmentioning
confidence: 99%
“…, and causes apoptosis and necrosis of cancer cells(Mocellin et al, 2005) Havunen et al (2017). engineered an OAd for expressing human IL-2 and TNF-α (Ad5/3-E2Fd24-hTNFa-IRES-hIL12 or TILT-123).…”
mentioning
confidence: 99%