Aurimune (CYT-6091) / CytImmune - LARVOL DELTA

Targeting poorly differentiated and anaplastic thyroid cancer microenvironment via TNF-α/TGF-β/LOX signaling to improve drug delivery and treatment efficacy (AACR 2022) - "We previously showed that the tumor microenvironment of poorly-differentiated (PDTC) and anaplastic thyroid cancer (ATC) can be selectively and effectively treated with nanomedicine carrying recombinant human Tumor Necrosis Factor α (TNFα)(CYT6091), resulting in vascular leakage, decreased IFP, and increased intratumoral concentration of paclitaxel in vivo. Moreover, TGF-β1 inhibition downregulates the protein levels of Smad3 molecules in thyroid cancer cells. TCGA database studies of thyroid cancer patient samples showed that SMAD3 positively correlated with TGFBR1 and LOX, suggesting the involvement of SMAD3 in TGF-β/LOX signaling in the TME."

Clinical • Endocrine Cancer • Oncology • Solid Tumor • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma • COL1A1 • LOX • SMAD3 • TGFB1 • TGFBR1 • TNFA

Novel Dual-Action Targeted Nanomedicine in Mice With Metastatic Thyroid Cancer and Pancreatic Neuroendocrine Tumors. (PubMed, J Natl Cancer Inst) - "Mice with metastatic FTC-133 and 8505C xenografts and the MEN1 conditional knock-out mice were treated weekly with CYT-21625 and gold nanoparticles with rhTNF only (CYT-6091); controls included mice treated with either paclitaxel or saline. CYT-21625 is effective in mice with PNETs and metastatic human thyroid cancer with no toxicities. Thus, CYT-21625 should be studied in patients with advanced PNETs and thyroid cancer."

Journal • Preclinical

Preclinical studies evaluate pivotal TNFα nanomedicine clinical trial design. (ASCO 2019) - "As part of the NCI’s Experimental Therapeutics (NExT) evaluation, CYT-6091 was studied in combination with paclitaxel (PTX) in C57BL/6 murine xenografts, using three cancer cell lines: MC-38 colon carcinoma (cancer cells sensitive to TNF, but insensitive to PTX), B16/F10 melanoma (cancer cells insensitive to TNF, but sensitive to PTX), Lewis lung carcinoma (cancer cells insensitive to both TNF and PTX), where sensitivity was based on inhibiting cancer cell growth at the studied dosing amounts and frequency. These preclinical studies demonstrate for the first time that CYT-6091 + PTX was superior to PTX (p < 0.01) or CYT-6091 alone (P < 0.05) in TNF insensitive cell lines, which represent the majority of cancers. Findings support systemically administering CYT-6091 plus standard-of-care chemotherapy in a pivotal clinical trial."