Clinical Cancer Research

Journal: Clinical Cancer Research

Abbreviation

Clin Cancer Res

Publisher

American Association for Cancer Research

ISSN

1078-0432
1557-3265

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Publications 1 - 10 of 32

Inhibition of rat mammary BN472 tumor growth is associated with a decrease in tumor (18)FDG uptake for the microtubule inhibitor patupilone but not the KDR/RAF inhibitor NVP-AAL881
McSheehy, P.M.; Allegrini, P.R.; Ametamey, Simon M.; et al. (2005)
Clinical Cancer Research
Fibroblast Activation Protein Triggers Release of Drug Payload from Non-internalizing Small Molecule Drug Conjugates in Solid Tumors
Zana, Aureliano; Galbiati, Andrea; Gilardoni, Ettore; et al. (2022)
Clinical Cancer Research
Purpose: Small molecule drug conjugates (SMDC) are modular anticancer prodrugs that include a tumor-targeting small organic ligand, a cleavable linker, and a potent cytotoxic agent. Most of the SMDC products that have been developed for clinical applications target internalizing tumor-associated antigens on the surface of tumor cells. We have recently described a novel non-internalizing small organic ligand (named OncoFAP) of fibroblast activation protein (FAP), a tumor-associated antigen highly expressed in the stroma of most solid human malignancies. Experimental Design: In this article, we describe a new series of OncoFAP-Drug derivatives based on monomethyl auristatin E (MMAE; a potent cytotoxic tubulin poison) and dipeptide linkers that are selectively cleaved by FAP in the tumor microenvironment. Results: The tumor-targeting potential of OncoFAP was confirmed in patients with cancer using nuclear medicine procedures. We used mass spectrometry methodologies to quantify the amount of prodrug delivered to tumors and normal organs, as well as the efficiency of the drug release process. Linkers previously exploited for anticancer drug conjugates were used as benchmark. We identified OncoFAP-Gly-Pro-MMAE as the best performing SMDC, which has now been prioritized for further clinical development. OncoFAP-Gly-Pro-MMAE selectively delivered more than 10% injected dose per gram of MMAE to FAP-positive tumors, with a tumor-to-kidney ratio of 16:1 at 24 hours post-injection. Conclusions: The FAP-specific drug conjugates described in this article promise to be efficacious for the targeting of human malignancies. The extracellular release of potent anticancer payloads mediates durable complete remission in difficult-to-treat animal models of cancer.
Immunoscintigraphic detection of the ED-B domain of fibronectin, a marker of angiogenesis, in patients with cancer
Santimaria, Monica; Moscatelli, Giovanni; Viale, Giuseppe L.; et al. (2003)
Clinical Cancer Research
In vivo Evaluation of 177Lu- and 67/64Cu-Labeled Recombinant Fragments of Antibody chCE7 for Radioimmunotherapy and PET Imaging of L1-CAM-Positive Tumors
Grünberg, Jürgen; Novak-Hofer, Ilse; Honer, Michael; et al. (2005)
Clinical Cancer Research
Radiotherapy of Human Sarcoma Promotes an Intratumoral Immune Effector Signature
Sharma, Anu; Bode, Beata; Studer, Gabriela; et al. (2013)
Clinical Cancer Research
In Vivo Imaging of Prostate Cancer Using [68Ga]-Labeled Bombesin Analog BAY86-7548
Kähkönen, Esa; Jambor, Ivan; Kemppainen, Jukka; et al. (2013)
Clinical Cancer Research
Antibody-radionuclide conjugates for cancer therapy
Steiner, Martina; Neri, Dario (2011)
Clinical Cancer Research
Mining Tissue Microarray Data to Uncover Combinations of Biomarker Expression Patterns that Improve Intermediate Staging and Grading of Clear Cell Renal Cell Cancer
Dahinden, Corinne; Ingold, Barbara; Wild, Peter; et al. (2010)
Clinical Cancer Research
Targeted Delivery of Tumor Necrosis Factor-α to Tumor Vessels Induces a Therapeutic T Cell–Mediated Immune Response that Protects the Host Against Syngeneic Tumors of Different Histologic Origin
Balza, Enrica; Mortara, Lorenzo; Sassi, Francesca; et al. (2006)
Clinical Cancer Research
Purpose: We sought to demonstrate that a single systemic administration of L19mTNFα (a fusion protein constituted by the scFv L19 specific for the oncofetal ED-B domain of fibronectin and tumor necrosis factor α, TNFα) in combination with melphalan induced complete and long-lasting tumor eradication in tumor-bearing mice and triggered the generation of a specific T cell–based immune response that protects the animals from a second tumor challenge, as well as from challenges with syngeneic tumor cells of different histologic origin. Experimental Design and Results: Treatment with L19mTNFα, in combination with melphalan, induced complete tumor regression in 83% of BALB/c mice with WEHI-164 fibrosarcoma and 33% of animals with C51 colon carcinoma. All cured mice rejected challenges with the same tumor cells and, in a very high percentage of animals, also rejected challenges with syngeneic tumor cells of different histologic origin. In adoptive immunity transfer experiments, the splenocytes from tumor-cured mice protected naive mice both from C51 colon carcinoma and from WEHI-164 fibrosarcoma. Similar results were also obtained in adoptive immunity transfer experiments using severely immunodepressed mice. Experiments using depleted splenocytes showed that T cells play a major role in tumor rejection. Conclusions: The results show that the selective targeting of mTNFα to the tumor enhances its immunostimulatory properties to the point of generating a therapeutic immune response against different histologically unrelated syngeneic tumors. These findings predicate treatment approaches for cancer patients based on the targeted delivery of TNFα to the tumor vasculature.
Enhanced Therapeutic Activity of Non-Internalizing Small-Molecule-Drug Conjugates Targeting Carbonic Anhydrase IX in Combination with Targeted Interleukin-2
Cazzamalli, Samuele; Ziffels, Barbara; Widmayer, Fontaine; et al. (2018)
Clinical Cancer Research

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