{"id":1204,"date":"2024-10-25T00:01:06","date_gmt":"2024-10-24T22:01:06","guid":{"rendered":"https:\/\/event.eortc.org\/ena2024\/?p=1204"},"modified":"2024-11-13T09:26:40","modified_gmt":"2024-11-13T08:26:40","slug":"new-mini-protien-radiation-dose","status":"publish","type":"post","link":"https:\/\/event.eortc.org\/ena2024\/2024\/10\/25\/new-mini-protien-radiation-dose\/","title":{"rendered":"New \u2018mini-protein\u2019 carries radiation dose directly to tumours without harming healthy tissues"},"content":{"rendered":"

Friday 25 October 2024, Barcelona, Spain: <\/strong>Researchers have shown for the first time that it is possible for a specially-designed \u2018mini-protein\u2019 to deliver a radiation dose directly to tumour cells expressing a protein on their cell surfaces called Nectin-4, which is often found in a number of different cancers.<\/p>\n

In a study presented on Friday at the 36th EORTC-NCI-AACR [1]<\/sup> Symposium on Molecular Targets and Cancer Therapeutics in Barcelona, Spain, Mike Sathekge, Professor and Head of the Nuclear Medicine Department at the University of Pretoria and Steve Biko Academic Hospital, South Africa, said he and his colleagues were able to show that the mini-protein, also known as a \u2018radiopharmaceutical\u2019, was able to target the cancer cells specifically, while avoiding healthy tissues, and that tumours in several different cancers absorbed the radiation dose.<\/p>\n

\u201cThis is the first time we are seeing a completely new technology used for targeted radiation. A small protein made to seek out a different protein that many cancers express, Nectin-4, was used to take radiation directly to the tumour,\u201d he said.<\/p>\n

The mini-protein is called AKY-1189 and is the first compound designed to deliver a therapeutic dose of Actinium-225, a radioactive element, by specifically targeting Nectin-4. This is a protein found in cell membranes and is over-expressed in up to 90% of patients with various solid tumours, including bladder, breast, lung, head and neck, cervical and bowel cancers.<\/p>\n

\u201cWe wanted to address the gap in care for patients whose cancer has grown beyond the part of the body it originated in or has spread to other parts of the body, and which had continued to progress on the local standard of care,\u201d said Prof. Sathekge.<\/p>\n

The researchers obtained permission for use of AKY-1189 under Section 21 under the South African Health Products Regulatory Authority (SAHPRA), and they imaged 20 patients at the Nuclear Medicine Research Infrastructure (NuMeRi), where Prof. Sathekge is president and CEO. Nine patients had metastatic bladder cancer, three had metastatic breast cancer, three had cervical cancer, two had colorectal cancer and three had non-small cell lung cancer.<\/p>\n

They gave the patients a single injection of AKY-1189 (~5mCi of [68Ga]Ga-AKY-1189), which is the amount used in routine imaging of radiopharmaceuticals. They scanned the patients after one, two and three hours using positron emission tomography-computed tomography (PET-CT) to assess how well the drug had targeted the tumours and how much of the dose the tumours had absorbed.<\/p>\n

In order to understand the dose over time (called \u2018dosimetry\u2019) that can be expected with [225Ac]Ac-AKY-1189 in tumours, organs, particularly the kidneys, and the whole body, the researchers injected AKY-1189 (10mCI [177Lu]Lu-AKY-1189) into nine patients and scanned them after three hours, 24 and 48 hours using SPECT-CT (single-photon emission computed tomography).<\/p>\n

So far, 15 patients have been available for the researchers to analyse how the drug was distributed through the body and how much was taken up by the tumours. Eight patients could be assessed to see if any effect on the kidneys would be predicted when patients receive actinium ([225Ac]Ac-AKY-1189) in the future.<\/p>\n

AKY-1189 did not have any adverse effects, including on the skin. The salivary glands showed a transient uptake that did not amount to any clinically meaningful exposure to radiation. The researchers found that there was some uptake of radiation in the kidneys, but at a level that suggests patients can safely receive a full course of [225Ac]Ac-AKY-1189 (six doses of ~8 MBq (megabequerels).<\/p>\n

The imaging showed substantial tumour uptake of the radiation in several different cancers, while any radiation disappeared rapidly from normal tissues.<\/p>\n

Prof. Sathekge said: \u201cThis was not a clinical trial and, therefore, we have not been able to collect data on cancer response to treatment yet, but those studies are now underway. However, we were able to gather important information not just for the specific patients, but also with respect to AKY-1189\u2019s potential for future patients. The most important learning from our work here is that we can clearly see that the drug is taken up by different types of tumours and, as such, has great potential for treating those patients\u2019 tumours. Also, and this is very important, we saw that the drug does not accumulate in normal tissue and so could be safe for multiple administrations to maximise treatment impact.<\/p>\n

\u201cThese data lay the foundation for further clinical research with the drug in metastatic bladder cancer and other tumours that have the Nectin-4 target. We are opening a study at our institute at NuMeRi in Pretoria, South Africa, for patients with metastatic breast, lung, colorectal, cervical, and bladder cancer. The company that developed AKY-1189, Aktis, is also preparing their study in the USA.\u201d<\/p>\n

Professor Timothy A Yap from the University of Texas MD Anderson Cancer Center, Houston, USA, is co-chair of the EORTC-NCI-AACR Symposium and was not involved in the research. He said: \u201cThis interesting study shows that it is possible for a unique \u2018mini-protein\u2019, AKY-1189, to target Nectin-4, a protein expressed in a number of different cancers, such as bladder, breast, lung, head and neck, cervical and bowel cancers. The imaging results presented today show how it is able to home in specifically on Nectin-4 with the radiation having little or no effect in other, healthy cells. These are the first results for AKY-1189 in humans, and we look forward to hearing the results from the forthcoming clinical trials in due course.\u201d<\/p>\n

Abstract no: 10<\/strong>, \u201cAKY-1189, a novel, first-in-class miniprotein radiopharmaceutical designed to deliver Actinium-225 (225Ac) to Nectin-4 expressing tumors with broad therapeutic applications in metastatic urothelial carcinoma (mUC) and other Nectin-4 expressing tumors\u201d, by Mike Sathekge, presented in the Proffered papers: new drugs on the horizon session, 12:00-13:30 hrs, Friday 25, October, Room 111+112.<\/p>\n

[1] EORTC [European Organisation for Research and Treatment of Cancer, NCI [National Cancer Institute], AACR [American Association for Cancer Research]. The Symposium takes place in Barcelona from 23-25 October 2024.<\/sup><\/p>\n

Funding: Aktis Oncology provided the drug for NuMeRI to use with radiation at no cost through the Section 21 programme of the South African Health Products Regulatory Authority (SAHPRA), an entity of the National Department of Health. NuMeRI is a non-profit organisation funded by Department of Science and Innovation.<\/sup><\/p>\n

The European Organisation for Research and Treatment of Cancer (EORTC), the USA\u2019s National Cancer Institute (NCI) and the American Association for Cancer Research (AACR) will join forces on 23-25 October 2024 to provide a platform for presenting recent advances in pre-clinical and clinical research. Around 1,300 international experts in the field will be discussing innovations in drug development, ground-breaking new data, the selection of new targets for anti-cancer drugs, and the impact of new discoveries in molecular biology, in order to improve the survival and quality of life of cancer patients.<\/sup><\/p>\n<\/div><\/div><\/div>

Recent posts<\/h4><\/div>
glyn<\/a><\/span><\/span>2024-11-13T09:26:15+01:00<\/span>

Scientists create cancer patients\u2019 \u2018digital twins\u2019 to predict how well treatments may work<\/a><\/h4>

Friday 25 October 2024, Barcelona, Spain: Researchers have shown that they can accurately re-create clinical trials of new treatments using \u2018digital twins\u2019 of real cancer patients. The technology, called FarrSight\u00ae-Twin, which is based on algorithms [...]<\/p><\/div><\/article>

glyn<\/a><\/span><\/span>2024-11-13T09:26:26+01:00<\/span>

Patients with advanced bladder cancer with alterations in the FGFR3 gene respond well to investigational drug, TYRA-300<\/a><\/h4>

Friday 25 October 2024, Barcelona, Spain: Patients with advanced bladder cancer that had spread to other parts of the body (metastasised) have responded well in a phase I clinical trial of an investigational drug, [...]<\/p><\/div><\/article>

glyn<\/a><\/span><\/span>2024-11-13T09:26:33+01:00<\/span>

Researchers find key genetic mutations in bowel cancer cells that lead to resistance to WRN inhibitors<\/a><\/h4>

Friday 25 October 2024, Barcelona, Spain: Researchers have discovered key mutations in certain cancer cells that make them resistant to WRN inhibitors, a new class of anti-cancer drugs. The yet-to-be-published findings are presented on Friday [...]<\/p><\/div><\/article>

glyn<\/a><\/span><\/span>2024-11-13T09:26:40+01:00<\/span>

New \u2018mini-protein\u2019 carries radiation dose directly to tumours without harming healthy tissues<\/a><\/h4>

Friday 25 October 2024, Barcelona, Spain: Researchers have shown for the first time that it is possible for a specially-designed \u2018mini-protein\u2019 to deliver a radiation dose directly to tumour cells expressing a protein on [...]<\/p><\/div><\/article>

glyn<\/a><\/span><\/span>2024-11-13T09:26:48+01:00<\/span>

Treatments used for HER2-positive breast cancers could help patients with rare gastrointestinal cancer<\/a><\/h4>

Trial of tucatinib and trastuzumab also showed benefits for HER2-mutated breast cancer: Thursday 24 October 2024, Barcelona, Spain: Drugs designed to target HER2-postive breast cancer could also benefit some patients with bile duct cancer, [...]<\/p><\/div><\/article>

frince<\/a><\/span><\/span>2024-11-13T09:26:57+01:00<\/span>

New drug, WNTinib, delays tumour growth and improves survival in mouse models of children\u2019s liver cancer<\/a><\/h4>

Wednesday 23 October 2024, Barcelona, Spain:\u00a0A new drug called WNTinib can delay the growth of tumours and improve survival in hepatoblastoma, a type of liver cancer that occurs in young children. This effect was [...]<\/p><\/div><\/article><\/section><\/div>

Share This Story<\/h4>
<\/i><\/a><\/span><\/i><\/a><\/span><\/i><\/a><\/span><\/div><\/div><\/div><\/div><\/div><\/div>\n","protected":false},"excerpt":{"rendered":"","protected":false},"author":5,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1],"tags":[],"class_list":["post-1204","post","type-post","status-publish","format-standard","hentry","category-uncategorized"],"_links":{"self":[{"href":"https:\/\/event.eortc.org\/ena2024\/wp-json\/wp\/v2\/posts\/1204","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/event.eortc.org\/ena2024\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/event.eortc.org\/ena2024\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/event.eortc.org\/ena2024\/wp-json\/wp\/v2\/users\/5"}],"replies":[{"embeddable":true,"href":"https:\/\/event.eortc.org\/ena2024\/wp-json\/wp\/v2\/comments?post=1204"}],"version-history":[{"count":0,"href":"https:\/\/event.eortc.org\/ena2024\/wp-json\/wp\/v2\/posts\/1204\/revisions"}],"wp:attachment":[{"href":"https:\/\/event.eortc.org\/ena2024\/wp-json\/wp\/v2\/media?parent=1204"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/event.eortc.org\/ena2024\/wp-json\/wp\/v2\/categories?post=1204"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/event.eortc.org\/ena2024\/wp-json\/wp\/v2\/tags?post=1204"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}