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ACTallo - Off-the-shelf Adoptive Cell Therapy
ACTallo® is a process developed by Immatics for the manufacture of allogeneic, off-the-shelf, TCR-engineered cellular therapies derived from healthy donors’ gamma delta T cells.
Immatics believes that gamma delta T cells are ideally suited for allogenic Adoptive Cell Therapy approaches because:
- gamma delta T cells naturally infiltrate tumors
- infiltration by gamma delta T cells has been shown to be the most favorable prognostic factor for patient outcome
- gamma delta T cells possess intrinsic antitumor activity and recognize target cells in an HLA/peptide independent fashion, not causing Graft-versus-Host Disease
Immatics has developed a process that allows ex vivo expansion of gamma delta T cells isolated from a single healthy donor to manufacture many ACTallo® doses, which Immatics believes represents an ideal modality for an off-the-shelf approach. Using healthy donor T cells circumvents the need to use T cells from heavily treated or aging cancer patients, thus allogeneic cells are not encumbered by suppressive environments of the patients´ immune system. In addition, products are available immediately for patient treatment without any delays for cellular manufacturing upon enrollment. At the laboratory scale, Immatics has observed that its proprietary manufacturing process could generate hundreds of doses from a single donor. Immatics is currently translating these lessons into larger scale solutions.
At the same time we are also committed to enhancing the potency of our ACT product candidates using several next-generation Technologies.
Targeting Tumor Stroma
The rigid stroma and the immunosuppressive microenvironment of solid tumors pose a significant challenge for T cell accessibility and activity. Targeting this compartment could provide a novel approach for the treatment of many solid tumors either as single attack or as part of a multi-TCT-T concept. Immatics’ fourth ACTengine® program IMA204 is directed against COL6A3 exon 6, a novel tumor stroma target identified and validated by Immatics’ XPRESIDENT® technology platform. COL6A3 exon 6 is highly expressed in the stroma of a variety of solid tumors. Thus, IMA204 is designed to disrupt the tumor’s protective microenvironment in order to make a therapeutic impact.
Multi-target Cell Therapy
Current challenges for effective cancer immunotherapies include tumor heterogeneity and tumor immune escape. Immatics aims to combat these limitations and to achieve deeper and longer clinical responses with its next-generation multi-TCR-T approach. To develop this approach, Immatics combines the expertise from the ACTolog® multi-target pilot study with the capability to engineer novel potent TCRs as used in the ACTengine® approach.
Immatics’ ACTolog® pilot trial (IMA-101-101) was the first step towards the implementation of a multi-TCR-T concept and showed clinical feasibility of a personalized multi-target approach against defined cancer targets. The ACTolog® concept is based on selecting and expanding a patient’s own non-engineered T cells dependent on the detection of ACTolog® targets in the patient’s tumor tissue. Results of this clinical pilot study support further exploration of a personalized ACT approach using T cells engineered with potent high-affinity TCRs as in Immatics’ lead product class ACTengine®.