Adenovirus Improves the Efficacy of Adoptive T-cell Therapy by Recruiting Immune Cells to and Promoting Their Activity at the Tumor

@article{Thtinen2015AdenovirusIT,
  title={Adenovirus Improves the Efficacy of Adoptive T-cell Therapy by Recruiting Immune Cells to and Promoting Their Activity at the Tumor},
  author={Siri T{\"a}htinen and Susanna Gr{\"o}nberg-V{\"a}h{\"a}-Koskela and Dave Lum{\'e}n and Maiju Merisalo-Soikkeli and Mikko Siurala and Anu J. Airaksinen and Markus V{\"a}h{\"a}-Koskela and Akseli Hemminki},
  journal={Cancer Immunology Research},
  year={2015},
  volume={3},
  pages={915 - 925}
}
Tähtinen and colleagues report that intratumoral injection of nonreplicating adenovirus can overcome immune tolerance and resistance of B16.OVA murine melanomas to T-cell therapy by recruitment and stimulation of tumor-infiltrating immune cells, thus improving the efficacy of adoptive T-cell therapy in solid tumors. Despite the rapid progress in the development of novel adoptive T-cell therapies, the clinical benefits in treatment of established tumors have remained modest. Several immune… 

Figures from this paper

Adenoviral Delivery of Tumor Necrosis Factor-α and Interleukin-2 Enables Successful Adoptive Cell Therapy of Immunosuppressive Melanoma.
TLDR
The results suggest the utility of cytokine-coding adenoviruses for improving the efficacy of adoptive T-cell therapies and suggest that mIL-2 has an important role in activating T-cells at the tumor, while mTNFα induces chemokine expression.
Oncolytic adenoviruses expressing transgenes targeting the tumor stroma to enhance the antitumor efficacy
TLDR
The data presented in this thesis strongly supports that the combination of viral oncolysis of cancer cells and FBiTE-mediated cytotoxicity of FAPexpressing CAFs might be an effective strategy to overcome a key limitation of on colytic virotherapy, encouraging its further clinical development.
T-Cell Therapy Enabling Adenoviruses Coding for IL2 and TNF&agr; Induce Systemic Immunomodulation in Mice With Spontaneous Melanoma
TLDR
Beneficial ratios between tumor-reactive PD-1+ CD8+ TILs and immunosuppressive cell subsets were observed in primary and secondary tumor sites, indicating that local delivery of IL2 and TNF&agr; coding adenoviruses can systemically modify the cellular composition of the tumor microenvironment in favor of adoptively transferred T cells.
Oncolytic Adenoviruses Armed with Tumor Necrosis Factor Alpha and Interleukin-2 Enable Successful Adoptive Cell Therapy
Adoptive T Cell Therapy Is Complemented by Oncolytic Virotherapy with Fusogenic VSV-NDV in Combination Treatment of Murine Melanoma
TLDR
Treatment with oncolytic VSV-NDV, combined with adoptive T cell therapy, induces multi-mechanistic and synergistic tumor responses, which supports the further development of this promising translational approach.
Syngeneic Syrian hamster tumors feature tumor-infiltrating lymphocytes allowing adoptive cell therapy enhanced by oncolytic adenovirus in a replication permissive setting
TLDR
The results support human translation of oncolytic adenovirus as an enabling technology for adoptive T-cell therapy of solid tumors and suggest systemic antitumor immunity was induced.
Systemic oncolytic adenovirus delivered in mesenchymal carrier cells modulate tumor infiltrating immune cells and tumor microenvironment in mice with neuroblastoma
TLDR
It was found that carrier cells outcompeted intravenous administration of naked particles in delivering the oncolytic virus into the tumor masses, and the protection that MSCs could provide to the on colytic adenovirus did not preclude the development of an antiadenoviral immune response.
CD40L coding oncolytic adenovirus allows long-term survival of humanized mice receiving dendritic cell therapy
TLDR
Results support clinical trials with Ad3-hTERT-CMV-hCD40L in patients receiving DC therapy and support the use of fully serotype 3 oncolytic adenovirus, expressing human CD40L, to modulate the tumor microenvironment with subsequently improved function of DCs.
Intravenously usable fully serotype 3 oncolytic adenovirus coding for CD40L as an enabler of dendritic cell therapy
TLDR
A novel adenovirus, Ad3-hTERT-CMV-h CD40L, which is fully serotype 3 and expresses hCD40L for induction of antitumor immune response is generated and is promising for translation into human trials and could enable successful dendritic cell therapy in cancer patients.
...
...

References

SHOWING 1-10 OF 60 REFERENCES
In situ adenovirus vaccination engages T effector cells against cancer.
Armed oncolytic virus enhances immune functions of chimeric antigen receptor-modified T cells in solid tumors.
TLDR
Preclinical data support the use of this innovative biologic platform of immunotherapy for solid tumors, using neuroblastoma as a tumor model and an oncolytic virus armed with the chemokine RANTES and the cytokine IL15 to facilitate migration and survival of CAR-T cells.
The In Vivo Therapeutic Efficacy of the Oncolytic Adenovirus Delta24-RGD Is Mediated by Tumor-Specific Immunity
TLDR
Delta24-RGD treatment led to long-term survival in 50% of mice and this effect was completely lost upon administration of the immunosuppressive agent dexamethasone, providing evidence that the immune system plays a vital role in the therapeutic efficacy of oncolytic adenovirus therapy of glioma.
Immunotherapy-induced CD8+ T cells instigate immune suppression in the tumor.
TLDR
It is discovered that the tumor adapts rapidly to the immune attack instigated by tumor-specific CD8+ T cells in the first few days following vaccination, resulting in the upregulation of a complex set of biological networks, including multiple immunosuppressive processes.
Adoptive T cell therapy promotes the emergence of genomically altered tumor escape variants
TLDR
The finding that T cells can directly promote genomic instability has important implications for the development of adoptive T cell therapies.
Oncolytic immunovirotherapy for melanoma using vesicular stomatitis virus.
TLDR
It is shown that CD8+ T cells are critical for the efficacy of intratumoral vesicular stomatitis virus virotherapy and are induced against both virally encoded and tumor-associated immunodominant epitopes.
Adoptive transfer of cytotoxic T lymphocytes targeting two different antigens limits antigen loss and tumor escape.
TLDR
It is found that early cotransfer could prevent tumor emergence in most mice, and simultaneous transfer of cytotoxic T lymphocytes targeted against two independent antigens would reduce selection for single-antigen-loss cells, thereby limiting tumor escape.
Chapter eight--Oncolytic adenoviruses for cancer immunotherapy: data from mice, hamsters, and humans.
Treatment of cancer patients with a serotype 5/3 chimeric oncolytic adenovirus expressing GMCSF.
TLDR
Ad5/3-D24-GMCSF seems safe in treating cancer patients and promising signs of efficacy were seen, and evidence of biological activity of the virus was seen in patients.
Multifactorial T-cell Hypofunction That Is Reversible Can Limit the Efficacy of Chimeric Antigen Receptor–Transduced Human T cells in Solid Tumors
TLDR
The results suggest that PD1 pathway antagonism may augment human CAR T-cell function, and will be an important tool for testing T cell–based strategies or systemic approaches to overcome this tumor-induced inhibition.
...
...