The melanoma-associated antigen A (MAGE-A) family is a subclass of cancer testis antigens expressed almost exclusively on healthy germline cells but also presented by MHC I on the surface of cells in a broad range of solid tumors.⁵ This makes these proteins ideal targets for cell therapies. Several clinical trials have examined the therapeutic potential of targeting MAGE-A3⁶, MAGE-A4 (for example, recently approved afami-cel), and MAGE-A10.⁷
First-in-human dose escalation trial of a MAGE-A1-directed TCR-T cell therapy for solid tumors
MHC Dextramer® reagents were used in the clinical trial to quantify MAGE-A1- specific T cells for dose determination
In July 2024, the cell therapy developer Immatics completed and published results from a phase I clinical trial assessing a TCR-based candidate directed at MAGE-A1.¹ MAGE-A1 had shown promise as a tumor-associated antigen in hepatocellular carcinoma2,3 and lung adenocarcinoma⁴, but Immatics is the first to examine MAGE-A1 in a clinical study.¹
The company’s IMA202 consists of autologous CD8+ T cells engineered to express a high-affinity TCR directed at a peptide derived from MAGE-A1. They enrolled patients with advanced or metastatic MAGE-A1-positive tumors and human leukocyte antigen haplotype HLA-A*02:01. A total of 16 patients received the treatment – seven with melanoma, three with squamous cell carcinoma, two with hepatocellular carcinoma, two with non-small cell lung cancer, and two patients with osteosarcoma and rhabdomyosarcoma respectively.
Accurate cell counts for dosing
A primary goal of the trial was to determine appropriate dosing.¹ Studies on solid tumors suggest that T cell dose may impact tumor infiltration and persistence of the cell product in the bloodstream.¹ Thus, the team at Immatics incorporated MHC Dextramer® reagents into their release testing to accurately detect and quantify transformed T cells.
To quote the study¹: “A comprehensive release testing was performed on each drug product for critical quality attributes, that is, safety, purity, identity, and quantity, and only passing products were released for infusion. MAGE-A1-specific T cells in the products were assessed by pHLA multimer staining (dextramer staining) for dose determination.”
The trial examined three dose levels starting at 50×106 transduced CD8+ T cells per m2 body surface area and then increasing to 300×106 and 1×107 cells per m2 body surface area. Even at the lowest dose, IMA202 showed long persistence in blood and infiltration of the target tissue. The number of cells infused correlated with peak persistence but not with infiltration rates. Based on insights from studies on other therapeutic cell types and targets, the team suggested that an increase in dose may lead to higher activity of IMA202. Overall, the trial demonstrated a manageable safety profile and no dose-limiting toxicities associated with IMA202.¹
Quality reagents for every stage
"Immatics uses Dextramer® reagents from Immudex for lot-release testing of TCR-based cell therapy product candidates. Being able to source high-quality pMHC multimer reagents from a reliable provider is important to us."
Kerry Sieger, M.A. Senior Director Global Quality Operations, Immatics
The U.S. Food & Drug Administration recommends direct detection of the engineered receptor transduced into T cells. Using Dextramer® reagents helps meet this regulatory guidance by allowing you to quantify the T cells that interact with the target allele/peptide. In this way, Dextramer® reagents can support the release testing of TCR-T cell therapies.
Our MHC Dextramer® reagents combine the right avidity, sensitivity, ease of use, and quality to support efficient assay development. Our portfolio of MHC Dextramer® reagents already includes a set of HLA-peptide complexes targeting MAGE-A1, one of which is already available as GMP. Our MHC Dextramer® GMP products meet all quality criteria and include an established shelf-life, expiry date, and certificate of analysis. The corresponding soluble TCR monomers and TCR Dextramer® reagents are also available via our Customer Solutions and Services team.
MAGE-A1 related MHC Dextramer®
MHC I Dextramer® |
Peptide |
Antigen |
Category |
Cat. No. |
| HLA-A*0101 | EADPTGHSY | MAGE-A1 | Melanoma | WA03248 |
| HLA-A*0201 | ALREEEEGV | MAGE-A1 | Melanoma | WB04476 |
| HLA-A*0201 | GTLEEVPTA | MAGE-A1 | Melanoma | WB06614 |
| HLA-A*0201 | KVLEYVIKV | MAGE-A1 | Melanoma | WB03474 |
| HLA-A*0301 | SLFRAVITK | MAGE-A1 | Cancer | WC06400 |
| HLA-A*2402 | NYKHCFPEI | MAGE-A1 | Melanoma | WF03738 |
| HLA-B*0702 | FPSLREAAL | MAGE-A1 | Melanoma | WH06468 |
| HLA-B*0702 | RVRFFFPSL | MAGE-A1 | Melanoma | WH03395 |
A selection of MHC Dextramer® reagents targeting MAGE-A1 available in our extensive product catalog.
Not finding the pHLA complex you need? Need reagents manufactured according to GMP? Our catalog continues to grow, and our experts are standing by to help.
Contact us and tell us about your project.
Learn more about Immudex products for the release testing of TCR-T cell therapies in this blog post.
References
¹ Wermke, M. et al. 2024. Journal for Immunotherapy of Cancer 12: e008668. doi: 10.1136/jitc-2023-008668
² Li, R. et al. 2020. Genomics 112: 5101. doi: 10.1016/j.ygeno.2020.09.026
³ Zerbini, A. et al. 2004. Journal of Hepatology 40: 102. Doi: 10.1016/S0168-8278(03)00484-7
⁴ Mao, Y. et al. 2019. Journal of Hematology & Oncology 12: 106. doi: 10.1186/s13045-019-0793-7
⁵ Schooten, E. et al. 2018. Cancer Treatment Reviews 67: 54–62. doi: 10.1016/j.ctrv.2018.04.009
⁶ Vansteenkiste, J. F. et al. The Lancet Oncology 17: 822–835. Doi: 10.1016/S1470-2045(16)00099-1
⁷ Hong, D. S. et al. 2022. Frontiers in Oncology 12: 818679. doi: 10.3389/fonc.2022.818679