Induction of potent systemic anti-melanoma immunity through intratumoral CD40 activation and checkpoint blockade

نویسندگان

  • Manisha Singh
  • Zhimin Dai
  • Hiep Khong
  • Christina Vianden
  • Mark Cantwell
  • Willem Overwijk
چکیده

Purpose Agonistic CD40 antibodies generate strong tumor specific CD8 T cell response and anti-tumor activity; however systemic anti-CD40 therapy has been associated with cytokine release syndrome and liver toxicity. We studied the anti-melanoma activity and mechanism of action of a recombinant adenovirus expressing a stabilized version of CD40L (rAd.CD40L) by local intratumoral delivery approach to treat metastatic melanoma.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Induction of systemic anti-melanoma immunity through intratumoral TLR-7/8 activation

Purpose Intratumoral immune activation can induce systemic immunity and anti-tumor activity. Imiquimod is a creamformulated, TLR-7 agonist that is FDA-approved for the treatment of non-melanoma skin cancers, but has limited activity against melanoma. In the current study, we studied the anti-tumor activity and mechanism of action of a novel injectable TLR 7/8 dual agonist, 3M-052, which remains...

متن کامل

Intratumoral modulation of the inducible co-stimulator ICOS by recombinant oncolytic virus promotes systemic anti-tumour immunity

Emerging data suggest that locoregional cancer therapeutic approaches with oncolytic viruses can lead to systemic anti-tumour immunity, although the appropriate targets for intratumoral immunomodulation using this strategy are not known. Here we find that intratumoral therapy with Newcastle disease virus (NDV), in addition to the activation of innate immunity, upregulates the expression of T-ce...

متن کامل

Microenvironment and Immunology Localized Immunotherapy via Liposome-Anchored Anti- CD137 þ IL-2 Prevents Lethal Toxicity and Elicits Local and Systemic Antitumor Immunity

Immunostimulatory agonists such as anti-CD137 and interleukin (IL)-2 have elicited potent antitumor immune responses in preclinical studies, but their clinical use is limited by inflammatory toxicities that result upon systemic administration. We hypothesized that by rigorously restricting the biodistribution of immunotherapeutic agents to a locally accessible lesion and draining lymph node(s),...

متن کامل

CD40 stimulation leads to effective therapy of CD40(-) tumors through induction of strong systemic cytotoxic T lymphocyte immunity.

Adequate spontaneous activation of tumor-specific T lymphocytes in tumor-bearing hosts is rare, despite the expression of tumor antigens that are potentially highly immunogenic. For example, failure of the immune system to raise competent responses against established tumors expressing the human adenovirus E1A-antigen allows this tumor to grow in immunocompetent mice. We show that systemic in v...

متن کامل

Transformation of the tumour microenvironment by a CD40 agonist antibody correlates with improved responses to PD-L1 blockade in a mouse orthotopic pancreatic tumour model

Despite the availability of recently developed chemotherapy regimens, survival times for pancreatic cancer patients remain poor. These patients also respond poorly to immune checkpoint blockade therapies (anti-CTLA-4, anti-PD-L1, anti-PD-1), which suggests the presence of additional immunosuppressive mechanisms in the pancreatic tumour microenvironment (TME). CD40 agonist antibodies (αCD40) pro...

متن کامل

ذخیره در منابع من

ذخیره در منابع من قبلا به منابع من ذحیره شده

{@ msg_add @}


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:

دوره 3  شماره 

صفحات  -

تاریخ انتشار 2015