On October 3, 2025 Ironfist Therapeutics ("Ironfist"), a preclinical-stage company developing a nanomedicine radiopharmaceutical (Tamrada) that selectively targets tumor associated macrophages without a targeting ligand, reported the company will be presenting positive preclinical proof of concept results in anti-PD-1 resistant triple negative breast (TNB) cancer models using 177Lu-Tamrada at the 38th Annual Congress of the European Association of Nuclear Medicine (EANM) (Press release, Ironfist Therapeutics, OCT 3, 2025, View Source [SID1234656446]).
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"These preclinical results coupled with our other 7 studies in a range of tumor types clearly demonstrate the therapeutic potential of targeting TAMs," said Jeffrey L Cleland, PhD, Chief Executive Officer of Ironfist Therapeutics.
TNB cancer is aggressive and unresponsive to anti-PD-1 antibody therapy in humans and preclinical models. Previous studies in the TNB cancer (4T1) mouse model presented at the Society for Nuclear Medicine and Molecular Imaging (SNMMI 2025) indicated a maximum 64Cu-Tamrada uptake of 41% ID/g in tumors. In this follow-up study, xenograft and orthotopic TNB cancer models were treated with the 177Lu-Tamrada at different radiation doses and regimens with and without anti-PD-1 antibody.
Key findings include:
Tamrada was tuned to optimize selectivity for TAMs and retention of 177Lu to maximize in vivo delivery to tumors
177Lu-Tamrada was retained in TAMs for over 10 days from a single administration (SPECT/CT)
177Lu-Tamrada alone caused tumor inhibition in both xenograft and orthotopic 4T1 mouse models
30 MBq 177Lu-Tamarada alone as a single or fractionated equivalent total dose (2x or 3x/week) caused significant (p < 0.05) tumor growth inhibition in orthotopic 4T1 tumor bearing mice compared to vehicle and anti-PD-1 treated mice.
At equivalent total radiation doses, fractionated doses were better tolerated and caused greater tumor accumulation than single doses.
"These preclinical results coupled with our other 7 studies in a range of tumor types clearly demonstrate the therapeutic potential of targeting TAMs," said Jeffrey L Cleland, PhD, Chief Executive Officer of Ironfist Therapeutics. "With this theragnostic approach, 64Cu/177Lu-Tamrada has the potential to precisely treat a wide range of tumors, kill tumor cells through bystander effects, and unlock the immune system. We look forward to sharing our compelling efficacy results in a PSMA negative mouse model at a subsequent meeting in 2026."
Unlike other radiopharmaceutical approaches, Tamrada is tumor agnostic because it is directly targeting TAMs. TAMs protect the tumor from the immune system, stimulate angiogenesis, and generate metastases. The hydroxyl dendrimer core of Tamrada was tuned specifically for selective uptake by TAMs without off target uptake in other macrophages. Once taken up by TAMs, Tamrada is not metabolized and is retained within the cells for up to one month providing a persistent source of radiation in the tumor with systemic clearance within 2-3 days.
Presentation Details:
Selective Killing of Tumor Associated Macrophages with a [177Lu]Lu-Nanomedicine Unlocks Checkpoint Inhibition
Presentation Number:
OP-025
Session Number:
204
Session Title:
M2M Track – TROP Session – Radiopharmaceutical Sciences + Translational
Molecular Imaging & Therapy Committee: New Targets in
Session Date:
Sunday, October 5, 2025
Session Presentation Time:
9:20:00 AM
Session Hall:
Room 114
About Tamrada
Tumors often enlist tumor-associated macrophages (TAMs) as protectors, shielding them from the immune system. Tamrada changes the story — reprogramming or removing these suppressive cells so the immune system can see the tumor clearly and strike with full force. Tamrada is designed from the novel nanomedicine technology of hydroxyl dendrimers invented at Johns Hopkins University. The nanomedicine component of Tamrada is comparable in size to an antibody fragment, does not leave the vasculature except in tumors, and has renal and biliary clearance without metabolism. 64Cu/177Lu-Tamrada enables precision dosing of cancer patients using a theragnostic approach. 177Lu-Tamrada provides an additional benefit of a bystander effect by killing adjacent tumor cells. The nanomedicine in Tamrada is amendable to modifications to create a pipeline of radiopharmaceuticals with different radioisotopes.