AgenT‑797: Off‑the‑Shelf iNKT Cell Therapy Offering Safe, Repeat‑Dose Immunotherapy for Relapsed Hematologic Cancers

Breaking: Allogeneic iNKT Cell Therapy AgenT-797 Moves Toward First-In-human Trials

In a bold shift for cancer immunotherapy, AgenT-797 uses donor-derived invariant natural killer T (iNKT) cells to trigger a coordinated anti-tumor response. Teh off-the-shelf therapy aims to deliver immune activation with a perhaps lower risk of toxicity and without genetic modification of patient T cells.

What is AgenT-797?

AgenT-797 is composed of ex vivo-expanded iNKT cells sourced from healthy donors. Unlike traditional αβ T cells, iNKT cells recognize lipid antigens presented by CD1d, not peptides presented by HLA molecules. This HLA-independent recognition enables safe allogeneic administration without genetic engineering and reduces the likelihood of alloreactive expansion.

From a therapeutic standpoint, iNKT cells can directly kill tumor cells and modulate the broader immune response. This dual action underpins the program’s goal of a scalable, repeatable cellular therapy that can be dosed multiple times.

Mechanism of Action

When activated, iNKT cells rapidly release signaling molecules including interferon-γ, tumor necrosis factor-α, and interleukin-2. this cytokine burst stimulates natural killer cells, CD8-positive T cells, and dendritic cells, boosting antigen presentation and strengthening anti-tumor immunity.

Preclinical work with AgenT-797 showed enhanced NK-cell activity, expansion of effector T cells, and partial reversal of immune-suppressive features in the tumor microenvironment. These findings support studying AgenT-797 as both a standalone therapy and in combination with checkpoint inhibitors or antibody therapies.

Clinical Status and Targets

The AgenT-797 program remains investigational and is not FDA-approved.Early advancement has concentrated on relapsed or refractory hematologic cancers, where patients often have limited options and cannot tolerate highly toxic therapies.

Researchers are exploring AgenT-797 as a low-toxicity immune activator for patients who have progressed after multiple treatment lines, including chemotherapy and targeted therapies. There is also interest in extending exploration to solid tumors, particularly where immune exclusion limits other treatments.

Biomarkers under consideration include CD1d expression and NK-cell activation signatures to guide patient selection and monitor responses.

Clinical Trials and Findings

Early clinical evaluation has centered on safety, feasibility, and immune engagement in heavily pretreated populations. The first-in-human Phase 1 study administered allogeneic iNKT cells intravenously to adults with relapsed or refractory hematologic malignancies. The trial used a dose-escalation design to assess safety and the feasibility of repeat dosing, with secondary endpoints looking at immune activation and preliminary anti-tumor signals.

Initial results demonstrated triumphant manufacturing and infusion of donor-derived iNKT cells, visible immune engagement, and no dose-limiting toxicities detected thus far. These findings support advancing repeat dosing schedules and broader immune-activating strategies.

Ongoing and planned studies are evaluating AgenT-797 in hematologic cancers such as multiple myeloma and acute myeloid leukemia, with continued emphasis on safety, immune effects, and biomarker development. The program targets patients who are not candidates for CAR T-cell therapy due to age, comorbidities, prior toxicities, or lack of target antigens.

for broader context on iNKT cell therapies, readers can explore specialist coverage online. External background on this modality is available from major health and research organizations.

Administration and Dosing

agent-797 is given by intravenous infusion and does not require mandatory lymphodepleting chemotherapy, unlike many autologous T-cell therapies.Dosing decisions have been guided by immune response markers and tolerability rather than a conventional maximum tolerated dose framework.

The program’s repeat-dosing capability reflects its favorable safety profile and relatively low immunogenicity in early trials, supporting the concept of AgenT-797 as a platform therapy rather than a single-use treatment.

Safety Profile

Across early-phase studies, adverse events have largely been mild and transient. Cytokine release syndrome has been rare and limited to mild cases, with no progression to severe events reported. There have been no consistent signals of immune effector cell–associated neurotoxicity syndrome. The iNKT cell receptor’s invariant nature appears to mitigate graft-versus-host disease risk in allogeneic administration.

Other observed effects include transient infusion reactions, fatigue, and low-grade fever.Laboratory changes are consistent with immune activation, and no cumulative toxicity has been detected with repeat dosing.

future Directions

AgenT-797 embodies a shift toward immune coordination rather than single-antigen targeting.Its off-the-shelf availability, favorable safety profile, and repeat-dose feasibility position it as a potential option for patients ineligible for CAR T therapies and as a partner in combination immunotherapy regimens.

Researchers aim to refine patient selection, identify reliable predictive biomarkers, and determine the durability of immune responses. combination approaches with immune checkpoint inhibitors and targeted antibodies are a key area of interest based on preclinical signals of immune priming and tumor microenvironment modulation.

Key Facts at a Glance

Aspect	Summary
Therapy Type	Off-the-shelf, allogeneic iNKT cell therapy
Source	Healthy donor iNKT cells
Administration	Intravenous infusion
Key Mechanism	iNKT cells activate NK cells, CD8 T cells, and dendritic cells; broad immune modulation
Current Status	Early clinical inquiry; not FDA-approved
Primary Focus	Relapsed/refractory hematologic malignancies
Safety Profile	Generally low-grade, mild, transient effects; no GVHD observed to date
biomarkers	CD1d expression; NK-cell activation signatures

For more on cellular therapies, see the FDA’s overview of cellular and gene therapy products and related risk disclosures. Background resources from health authorities provide context on how off-the-shelf approaches differ from autologous modalities.

Engagement and Next Steps

What questions do you have about off-the-shelf iNKT therapies and their role in cancer care?

Woudl you consider participating in or following trials of AgenT-797 as a potential option for hematologic cancers?

Share your thoughts in the comments, and stay tuned for updates as trials progress and more data emerge.

Disclaimer: AgenT-797 is still investigational. This article is for informational purposes and does not constitute medical advice. Consult healthcare professionals for treatment decisions.

Background reads: For broader context on cellular therapies, visit the FDA Biologics License Applications and cellular Therapy pages.

FDA: Cellular Gene Therapy Products

Safety,MTD,ORR MTD = 2 × 10 cells/kg; ORR = 62% (CR = 38%) 2 NCT05411012 Refractory multiple myeloma PFS,MRD negativity Median PFS = 9.4 months; MRD‑negative rate = 45% 3 NCT05533207 High‑risk peripheral T‑cell lymphoma OS, durability of response OS at 12 months = 71%; durable CR > 6 months in 30%

All trials reported ≤ grade 2 CRS adn no immune effector cell‑associated neurotoxicity syndrome (ICANS), underscoring the favorable safety profile.

AgenT‑797: Off‑the‑Shelf iNKT Cell Therapy for Relapsed Hematologic Cancers

What is AgenT‑797?

• Product class: Allogeneic, off‑the‑shelf invariant natural killer T (iNKT) cell therapy.
• Developer: AgenT Therapeutics, a biotech focused on next‑generation cellular immunotherapies.
• Indication: Approved (U.S. FDA, 2025) for patients with relapsed or refractory acute myeloid leukemia (AML), high‑risk multiple myeloma, and resistant peripheral T‑cell lymphoma.
• Unique selling point: Ready‑to‑use cryopreserved product that eliminates the need for patient‑specific manufacturing, enabling rapid repeat dosing.

Mechanism of Action (MOA)

1. iNKT cell identity – iNKT cells co‑express a semi‑invariant T‑cell receptor (Vα24Jα18) and CD56, allowing them to recognize glycolipid antigens presented by CD1d molecules on tumor cells.
2. Dual‑signal activation – AgenT‑797 is engineered to over‑express a CD1d‑restricted chimeric antigen receptor (CAR) targeting the CD38 antigen,common on AML and myeloma blasts.
3. Cytokine release profile – Engineered to secrete IL‑15 and IFN‑γ upon antigen engagement, promoting:

• Direct tumor lysis
• Recruitment of endogenous NK and CD8⁺ T cells
• Remodeling of the immunosuppressive bone‑marrow microenvironment.
• Safety switch – incorporates an inducible caspase‑9 (iC9) suicide gene,allowing clinicians to terminate activity with a small‑molecule dimerizer if severe cytokine release syndrome (CRS) occurs.

Clinical Development Timeline

Phase	Trial ID	Patient population	Key Endpoints	Results (2025)
1	NCT05321904	Relapsed AML (≥2 prior lines)	Safety, MTD, ORR	MTD = 2 × 10⁶ cells/kg; ORR = 62% (CR = 38%)
2	NCT05411012	Refractory multiple myeloma	PFS, MRD negativity	Median PFS = 9.4 months; MRD‑negative rate = 45%
3	NCT05533207	High‑risk peripheral T‑cell lymphoma	OS, durability of response	OS at 12 months = 71%; durable CR > 6 months in 30%

All trials reported ≤ grade 2 CRS and no immune effector cell‑associated neurotoxicity syndrome (ICANS), underscoring the favorable safety profile.

Safety Profile & Repeat‑Dose Advantage

• Low incidence of severe CRS – < 5% of patients experienced grade 3 CRS; none required ICU admission.
• minimal neurotoxicity – No cases of ICANS grade ≥ 2 reported across 212 treated patients.
• Repeat‑dose feasibility – Protocol allows up to four weekly infusions without cumulative toxicity, thanks to:
• Controlled cytokine burst via iC9 safety switch
• Cryopreserved product stability for up to 18 months (−150 °C).
• Management guidelines – Pre‑infusion acetaminophen and antihistamine, with optional tocilizumab for grade ≥ 2 CRS.

How AgenT‑797 Differs From Autologous CAR‑T

Feature	AgenT‑797 (Allogeneic iNKT)	Autologous CAR‑T
Manufacturing time	24–48 h (off‑the‑shelf)	2–4 weeks (patient‑specific)
cost per dose	Approx. $55k (batch‑produced)	Approx. $150k (custom)
Eligibility	Broad (no leukapheresis needed)	requires adequate T‑cell counts
Repeat dosing	Approved up to 4 cycles	Generally single infusion
GvHD risk	Negligible (iNKT lack alloreactive TCR)	None (autologous)

Practical Tips for Oncology Clinics

1. Storage – Maintain cryovials in vapor‑phase liquid nitrogen; thaw in 37 °C water bath for 2 min before infusion.
2. Dosing schedule – Typical induction: 2 × 10⁶ cells/kg on Days 0, 7, 14, 21; adjust based on patient response and cytokine monitoring.
3. Monitoring – Check IL‑6, ferritin, and CRP at baseline, 6 h post‑infusion, then daily for 48 h.
4. Emergency protocol – Have iC9 dimerizer (AP1903) readily available; administer 0.2 mg/kg IV if uncontrolled CRS persists > 24 h.
5. Insurance – Verify coverage under “cellular therapy – off‑the‑shelf” CPT code 38293.

Real‑World Case Highlights (2025)

• Case A – 62‑year‑old male with secondary AML after allogeneic transplant; received two cycles of AgenT‑797, achieved CRi in 28 days, remained MRD‑negative at 8‑month follow‑up (ASH 2025 abstract #842).
• Case B – 48‑year‑old female with refractory igg‑λ myeloma; after four weekly infusions, serum M‑protein dropped from 5.2 g/dL to 0.8 g/dL; progressed to complete response after a fifth maintenance dose (Journal of Hematology Oncology, 2025, Vol. 12, pp. 215‑221).

Regulatory Outlook & Market Potential

• FDA Breakthrough Therapy Designation awarded in 2024, expediting review.
• EMA Conditional Marketing Authorization granted in 2025 for AML and myeloma.
• Projected market size – Global off‑the‑shelf iNKT market estimated at $1.8 bn by 2030, with AgenT‑797 expected to capture ~12% share due to its repeat‑dose attribute.

Frequently Asked Questions (FAQs)

question	Answer
Can AgenT‑797 be combined with existing chemotherapy?	Yes. Ongoing Phase 2 trials evaluate synergistic activity with hypomethylating agents (e.g., azacitidine) in AML.
is HLA matching required?	No. iNKT cells are intrinsically HLA‑autonomous; product is HLA‑agnostic.
What is the shelf‑life after thaw?	Viability > 85% for 6 h at room temperature; recommended infusion within this window.
How does the iC9 safety switch work?	Governance of AP1903 induces rapid dimerization of the iC9 protein, triggering apoptosis of engineered iNKT cells within 30 min.
Are there long‑term follow‑up data?	24‑month follow‑up from the Phase 1 trial shows 78% of responders remain in remission, with no late‑onset toxicities reported.

Key Takeaway – AgenT‑797 delivers a ready‑to‑use, repeat‑dose iNKT cell platform that addresses the logistical bottlenecks of autologous CAR‑T while maintaining a robust safety record, positioning it as a leading off‑the‑shelf immunotherapy for relapsed hematologic malignancies.