Correction: Preclinical Development of Ipilimumab and Nivolumab Combination Immunotherapy: Mouse Tumor Models, In Vitro Functional Studies, and Cynomolgus Macaque Toxicology

Selby, Mark; Engelhardt, John J.; Johnston, Robert J.; Liu, Lisheng; Han, Meekyung; Thudium, Kent; Yao, Dapeng; Quigley, Michael; Valle, Jose; Wang, Changyu; Chen, Bing; Cardarelli, Pina M.; Blanset, Diann

doi:10.1371/journal.pone.0167251

Cited by 27 publications

(7 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Benchmark can result in robust tumor growth inhibition [9,10]. In contrast, in a relatively cold tumor model such as B16F10, we do not see efficacy with anti-CTLA4 treatment (Fig.…”

Section: Pol Scientificmentioning

confidence: 71%

Generation of bone marrow chimeras using X-ray irradiation: comparison to cesium irradiation and use in immunotherapy

Eng

Orf

Perez

et al. 2020

JBM

View full text Add to dashboard Cite

Bone marrow chimeras represent a key tool employed to understand biological contributions stemming from the hematopoietic versus the stromal compartment. In most institutions, cesium irradiators are used to lethally irradiate recipient animals prior to the injection of donor bone marrow. Cesium irradiators, however, have significant liabilities-including concerns around domestic security. Recently, X-ray irradiators have been implemented as a potential alternative to cesium sources. Only a small number of publications in the literature have attempted to compare these two modalities and, in most cases, the emphasis was on irradiation of human blood productions. We were able to find only a single study that directly compared X-ray and cesium technologies in the generation of murine bone marrow chimeras, a standard laboratory practice. This study focused on chimerism in the blood of recipient animals. In the present study, we begin by comparing cesium and X-ray based sources for irradiation, then transition to using X-ray-based systems for immunology models with an emphasis on immunotherapy of cancer in immunocompetent mouse models-specifically evaluating chimerism in the blood, spleen, and tumor microenvironment. While our data demonstrate that the two platforms are functionally comparable and suggest that X-ray based technology is a suitable alternative to cesium sources. We also highlight a difference in chimerism between the peripheral (blood, spleen) and tumor compartments that is observed using both technologies. While the overall degree of chimerism in the peripheral tissues is very high, the degree of chimerism in the tumor is cell type specific with T and NK cells showing lower chimerism than other cell types.

show abstract

“…Benchmark can result in robust tumor growth inhibition [9,10]. In contrast, in a relatively cold tumor model such as B16F10, we do not see efficacy with anti-CTLA4 treatment (Fig.…”

Section: Pol Scientificmentioning

confidence: 71%

Generation of bone marrow chimeras using X-ray irradiation: comparison to cesium irradiation and use in immunotherapy

Eng

Orf

Perez

et al. 2020

JBM

View full text Add to dashboard Cite

show abstract

“…This combination received accelerated approval based on median PFS in the Phase III ‘CHECKMATE-067’ clinical trials (Table 7). The results of this trial of 945 previously untreated patients demonstrated a significant improvement in median PFS in patients with advanced melanoma treated with the combination therapy and with nivolumab alone, compared with ipilimumab alone ( p < 0.0001 and p < 0.0001, respectively) [323]. Therefore, these preliminary trials highlight the therapeutic potential of this type of combination approach for the treatment of cancer.…”

Section: Discussionmentioning

confidence: 99%

Clinical development of targeted and immune based anti-cancer therapies

Seebacher

Stacy

Porter

et al. 2019

J Exp Clin Cancer Res

197

131

View full text Add to dashboard Cite

Cancer is currently the second leading cause of death globally and is expected to be responsible for approximately 9.6 million deaths in 2018. With an unprecedented understanding of the molecular pathways that drive the development and progression of human cancers, novel targeted therapies have become an exciting new development for anti-cancer medicine. These targeted therapies, also known as biologic therapies, have become a major modality of medical treatment, by acting to block the growth of cancer cells by specifically targeting molecules required for cell growth and tumorigenesis. Due to their specificity, these new therapies are expected to have better efficacy and limited adverse side effects when compared with other treatment options, including hormonal and cytotoxic therapies. In this review, we explore the clinical development, successes and challenges facing targeted anti-cancer therapies, including both small molecule inhibitors and antibody targeted therapies. Herein, we introduce targeted therapies to epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), human epidermal growth factor receptor 2 (HER2), anaplastic lymphoma kinase (ALK), BRAF, and the inhibitors of the T-cell mediated immune response, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein-1 (PD-1)/ PD-1 ligand (PD-1 L).

show abstract

“…Here, our immunoPET study sought to quantify tumor infiltrating CD8 + T-cells after single or combination immunotherapy with CpG and αPD-1. CpG triggers an immunomodulatory response that expands CD8 + T-cells (58,59) and αPD-1, an immune check-point inhibitor, increases the frequency of tumor infiltrating CD8 + T-cells (60,61). In our results from CD8 IHC staining of tumors, CD8 + T-cells were more evident in tumors from treated mice than in tumors from NT mice.…”

Section: Effects Of Multi-dose Immunotherapy On Perfusion and Tumor Vmentioning

confidence: 99%

CD8+ T-Cell Density Imaging with 64Cu-Labeled Cys-Diabody Informs Immunotherapy Protocols

Seo

Tavaré

Mahakian

et al. 2018

Clinical Cancer Research

View full text Add to dashboard Cite

Noninvasive and quantitative tracking of CD8 T cells by PET has emerged as a potential technique to gauge response to immunotherapy. We apply an anti-CD8 cys-diabody, labeled with Cu, to assess the sensitivity of PET imaging of normal and diseased tissue. Radiolabeling of an anti-CD8 cys-diabody (169cDb) with Cu was developed. The accumulation ofCu-169cDb was evaluated with PET/CT imaging (0, 5, and 24 hours) and biodistribution (24 hours) in wild-type mouse strains ( = 8/group studied with imaging and IHC or flow cytometry) after intravenous administration. Tumor-infiltrating CD8 T cells in tumor-bearing mice treated with CpG and αPD-1 were quantified and mapped ( = 6-8/group studied with imaging and IHC or flow cytometry). We demonstrate the ability of immunoPET to detect small differences in CD8 T-cell distribution between mouse strains and across lymphoid tissues, including the intestinal tract of normal mice. In FVB mice bearing a syngeneic -driven model of mammary adenocarcinoma (NDL),Cu-169cDb PET imaging accurately visualized and quantified changes in tumor-infiltrating CD8 T cells in response to immunotherapy. A reduction in the circulation time of the imaging probe followed the development of treatment-related liver and splenic hypertrophy and provided an indication of off-target effects associated with immunotherapy protocols. Cu-169cDb imaging can spatially map the distribution of CD8 T cells in normal organs and tumors. ImmunoPET imaging of tumor-infiltrating cytotoxic CD8 T cells detected changes in T-cell density resulting from adjuvant and checkpoint immunotherapy protocols in our preclinical evaluation. .

show abstract

Correction: Preclinical Development of Ipilimumab and Nivolumab Combination Immunotherapy: Mouse Tumor Models, In Vitro Functional Studies, and Cynomolgus Macaque Toxicology

Cited by 27 publications

References 1 publication

Generation of bone marrow chimeras using X-ray irradiation: comparison to cesium irradiation and use in immunotherapy

Generation of bone marrow chimeras using X-ray irradiation: comparison to cesium irradiation and use in immunotherapy

Clinical development of targeted and immune based anti-cancer therapies

CD8+ T-Cell Density Imaging with 64Cu-Labeled Cys-Diabody Informs Immunotherapy Protocols

Contact Info

Product

Resources

About