90Y-NM600 / Archeus Technologies - LARVOL DELTA

Combining tumor-specific vaccination with radiopharmaceutical therapy (RPT) enhances anti-tumor response in OVA-expressing tumor model (SITC 2024) - "90Y-NM600 is an RPT agent targeting the lipid rafts of tumors, shown to modulate the tumor immune microenvironment...Conclusions Tumor-specific CD8+ T cells need to ideally be present and activated prior to RPT for greater anti-tumor efficacy, suggesting that anti-tumor vaccination should be delivered prior to RPT. Future studies will explore the role of vaccination post-RPT to maintain T cell infiltration and affect T cell function."

Preclinical • Oncology • CD8

Tumor Immunity Following Radiopharmaceutical + Checkpoint Blockade Varies with Treatment Sequence, Radioisotope and Tumor Immunogenicity (ASTRO 2024) - "90Y-NM600+ICI produced the greatest anti-tumor response for MC38, whereas high LET alpha particle radiation from 225Ac-NM600 was most effective with ICIs against the poorly immunogenic B78 model... Antitumor immune response can be achieved with appropriate application of a- or ß- emitting RPT in combination with ICIs in diverse murine tumor models."

Checkpoint block • Checkpoint inhibition • Colorectal Cancer • Gastrointestinal Cancer • Melanoma • Oncology • Solid Tumor • CD8 • PTPRC

Myeloid-derived suppressor cells attenuate the antitumor efficacy of radiopharmaceutical therapy using 90Y-NM600 in combination with androgen deprivation therapy in murine prostate tumors. (PubMed, J Immunother Cancer) - "The combination of ADT and TRT improved antitumor responses in murine models of prostate cancer, however, this was dependent on the order of administration. This was found to be associated with one treatment sequence leading to an increase in infiltrating MDSCs. Combining treatment with a CXCR2 antagonist improved the antitumor effect of this combination, suggesting a possible approach for treating advanced human prostate cancer."

Combination therapy • Journal • Myeloid-derived suppressor cells • Preclinical • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • CD4 • CD8 • CXCL1 • CXCR2

Radionuclide-specific effects of90Y-,177Lu-, or225Ac-NM600 targeted radionuclide therapy on tumor immunomodulation and enhanced immunotherapy response in syngeneic murine tumors (AACR 2023) - "We previously showed that low dose radiation delivery with 90Y-NM600 improves tumor response to immune checkpoint inhibitors (ICIs)... The distinct physical properties of TRT radiation, γ, β or α, affect the timing, magnitude, and molecular pathways leading to this IFN1 response. Understanding TRT effects on the tumor microenvironment may optimize TRT and immunotherapy."

Immunomodulating • IO biomarker • Preclinical • Melanoma • Oncology • Solid Tumor • DDX58 • IFNB1 • STING

Radionuclide-specific effects of 90Y-, 177Lu-, or 225Ac-NM600 targeted radionuclide therapy on tumor immunomodulation and enhancing immunotherapy response in murine tumor models (AACR 2022) - "Purpose: In preclinical studies, we have demonstrated that delivering low dose radiation to all tumor sites utilizing 90Y-NM600 improves the response to immune checkpoint inhibitors (ICIs)... These studies demonstrate the capacity to deliver immunomodulatory radiation to tumors using gamma-, beta- or alpha-emitting TRT. The physical properties of the delivered radionuclide dictate timing and magnitude of the IFN1 response stimulated by TRT. Understanding these effects may be critical to safely and effectively integrating TRT and immunotherapies to enhance anti-tumor immunity in cancer patients."

IO biomarker • Preclinical • Head and Neck Cancer • Melanoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD8 • IFNB1 • STING

Combination of antigen-specific vaccination and targeted radionuclide therapy improves anti-tumor efficacy in a murine prostate model (SITC 2021) - "Background While checkpoint blockade has been unsuccessful in prostate cancer trials, the approval of Sipuleucel-T demonstrates the value of antigen-specific vaccination approaches for this disease...An intravenous injection was administered of 50 (”low-dose”) or 250 μCi (”high dose”) of 90Y-NM600, estimated to deliver a dose of 3.1 Gy or 15.5 Gy to 300 mm3 tumors, respectively...Conclusions These data suggest that the combination of antigen-specific vaccination and TRT can be an effective treatment for cancers that are refractory to immunotherapy. This combination may act through increasing co-stimulation by dendritic cells, leading to a more active cytolytic CD8+ T cell population."

IO biomarker • Preclinical • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • AR • CD8 • CD86 • PD-1 • TIGIT

Safety and feasibility of an in situ vaccination and immunomodulatory targeted radionuclide combination immuno-radiotherapy approach in a comparative (companion dog) setting. (PubMed, PLoS One) - "The combination of external beam radiotherapy, intratumoral immunocytokine, and targeted radionuclide immuno-radiotherapy known to have activity against syngeneic melanoma in murine models is feasible and well tolerated in companion dogs with advanced stage, spontaneously arising melanoma or osteosarcoma and has immunomodulatory potential. Further studies evaluating the dose-dependent immunomodulatory effects of this immuno-radiotherapy combination are currently ongoing."

Clinical • Journal • Hematological Malignancies • Immune Modulation • Immunology • Inflammation • Melanoma • Oncology • Sarcoma • Solid Tumor • IL2

[VIRTUAL] Mechanisms of cooperative response to bempegaldesleukin (BEMPEG) and 90Y-NM600 targeted radionuclide therapy in the treatment of a syngeneic murine model of head and neck squamous cell carcinoma (AACR 2021) - "These results suggest a synergistic interaction between BEMPEG and 90Y-NM600 that improves the immune microenvironment in this difficult to treat murine model of HNSCC, which may thereby enhance the response to immune checkpoint blockade. Further studies are warranted to examine the therapeutic implications of this combination in patients."

IO biomarker • Preclinical • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD22 • CD8 • CSF1 • CXCL10 • CXCL11 • CXCL9 • IL17A • IL2 • IL4 • IL5 • PD-L1 • TNFA

[VIRTUAL] Temporal analysis of type 1 interferon activation in tumor cells following external beam radiotherapy or targeted radionuclide therapy (AACR 2021) - "Tumor-specific dosimetry for 90Y-NM600 was determined using sequential 86Y-NM600 PET/CT imaging (3h, 24h, 48h, 72h) and a Monte Carlo based dose calculation platform... We report the time course of the STING-dependent IFN1 response following RT in multiple murine tumor models. We show the potential of TRT to stimulate IFN1 activation that is comparable to that observed with EBRT of equivalent cumulative dose. Further evaluation of the timing and magnitude of IFN1 response following EBRT and TRT may be critical to the optimal integration with immunotherapies."

IO biomarker • Head and Neck Cancer • Melanoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

[VIRTUAL] In vivo synergy of 90Y-NM600 and Bempegaldesleukin improves anti-tumor efficacy of immune checkpoint inhibitors in syngeneic murine cancer models (AACR 2021) - "Combination of 90Y-NM600, BEMPEG, and ICI displays robust anti-tumor activity that prevents metastatic disease progression and prolongs survival in spontaneously metastatic, immunologically “cold” tumor models. Clinical studies are warranted to test the safety and efficacy of this promising combined modality treatment regimen."

Checkpoint inhibition • Preclinical • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD22 • IL2