Adoptive Neoantigen activated T Cell Transfer Therapy Solution

Adoptive Neoantigen-activated T Cell Transfer (ACT) Therapy Solution

Creative Biolabs is a global leader in high-precision cancer immunotherapy, offering an integrated, end-to-end preclinical platform for the development of adoptive neoantigen-activated T cell transfer (ACT) therapy. Our mission is to transform the promise of personalized medicine into actionable cell products. By combining high-resolution multi-omics profiling with advanced ex vivo T cell enrichment and high-throughput TCR discovery, we provide researchers with the tools to overcome tumor heterogeneity and achieve potent, antigen-specific antitumor responses in preclinical models.

Pioneering the Future of Precision Immunotherapy: NRT Platform

The Power of Neoantigen-Reactive T cells (NRTs)

Unlike standard ACT which often relies on non-specific tumor-infiltrating lymphocytes (TILs), our Neoantigen-Reactive T cell (NRT) solution focuses exclusively on T cells that recognize tumor-specific mutations. This specificity ensures high potency while minimizing the risk of "off-target" toxicity against normal tissues. Our platform bridges the gap between bioinformatics prediction and functional cell product generation, supporting both non-engineered NRT enrichment and TCR-T engineering routes.

Why Focus on Neoantigen-Specific T Cells?
Neoantigens are unique to the tumor and bypass central tolerance. By selectively activating and expanding NRTs, we harness a diverse TCR repertoire capable of multi-target recognition, which is essential for combating the immunosuppressive tumor microenvironment and preventing antigen escape.

Core Preclinical Challenges We Address:
Accurate identification of low-frequency neoantigen-reactive clones.
Parallel expansion strategies utilizing both PBMC and TIL sources.
High-throughput TCRα/β pairing and functional ranking.
Comprehensive in vitro and in vivo potency assessment.

Harnessing the Full Potential of Tumor-Reactive T Cells

Feature Comparison	Traditional ACT (TIL-based)	Neoantigen-Activated ACT (NRT-based)
Antigen Specificity	Mixed; high proportion of "bystander" T cells.	Highly specific to tumor-exclusive neoepitopes.
Target Selection	Uncertain; depends on natural infiltration.	Rationally designed based on omics & prediction.
Safety Profile	Risk of cross-reactivity with normal self-antigens.	Superior safety; targets are absent in normal tissue.
Therapeutic Durability	Often limited by clonal exhaustion.	Enhanced through selective polyfunctional priming.

Comprehensive Service Portfolio for Preclinical ACT Development

Neoantigen Discovery & Prioritization

Building the blueprint for target-specific T cell activation.

Matched Tumor-Normal WES/RNA-seq for somatic mutation calling.
HLA typing and MHC class I/II binding prediction.
Transcription verification and expression filtering.
Advanced ranking based on clonality and WT vs. Mut peptide distance.

NRT Induction & Enrichment

Turning predicted epitopes into reactive T cell populations.

Preparation of SLP pools, tandem minigenes, or mRNA vectors.
Co-culture with autologous DCs or engineered artificial APCs (aAPCs).
Multi-marker enrichment (CD137, CD134, PD-1, Tetramer/Multimer).
Parallel processing of TILs and peripheral blood PBMCs.

High-Throughput TCR Discovery

Identifying the molecular assets for next-gen TCR-T development.

Comprehensive TCRα/β repertoire profiling at both population and individual cell resolutions.
Function-associated transcriptomics at cellular resolution to identify superior T cell states.
TCR cloning and validation of cross-reactivity risks.
Database-driven TCR ranking for polyfunctional persistence.

In Vitro & In Vivo Potency Assessment

Rigorous validation of therapeutic efficacy and durability.

Cytotoxicity assays (serial killing, 3D tumor spheroids/organoids).
Cytokine profiling (IFN-γ ELISpot, ICS, Luminex).
Efficacy in syngeneic, humanized, or PDX tumor models.
Monitoring of persistence, trafficking, and preliminary safety.

Integrated Workflow for Neoantigen-Specific T Cell Generation

Integrated workflow for Neoantigen ACT development

Phase 1 — Project Initiation & Neoantigen Discovery

Utilizing tumor and paired normal tissue (or PBMC), we conduct WES/RNA-seq for somatic mutation identification. This phase identifies tumor-exclusive epitopes and prioritizes them based on HLA binding affinity, expression strength, and drugability paths.

Phase 2 — Screening Toolkit Development

We synthesize customized toolkits including peptide pools (short/long peptides), tandem minigenes, or mRNA vectors. These tools are used for autologous DC loading or aAPC engineering to create a robust stimulation environment.

Phase 3 — NRT Induction & Multi-Marker Enrichment

T cells from TIL or peripheral blood are co-cultured with antigen-loaded APCs. Reactive clones are enriched using high-resolution markers (CD137, CD134, PD-1) or tetramer-based magnetic sorting for specific subset profiling.

Phase 4 — TCR Discovery & Engineering (Optional Route)

For TCR-T development, we perform high-throughput population-level or individualized cellular TCR repertoire analysis (α/β dual-chain reconstruction). This enables the selection of superior neoTCRs through integrated functional profiling while minimizing the risk of cross-reactivity.

Phase 5 — In Vivo Potency & Efficacy Evaluation

Enriched NRTs or engineered TCR-T cells undergo in vivo testing in syngeneic or humanized tumor models. We provide detailed reports on tumor regression, TIL density, and cellular persistence to support preclinical translation.

Enabling Technologies for High-Efficiency Neoantigen ACT

High-Throughput scTCR Discovery

A synergistic framework combining transcriptomic profiling and TCRα/β dual-chain reconstruction at cellular resolution to pinpoint rare, high-potency reactive lineages in peripheral blood or TILs, ensuring precise mapping of clonal identity to functional states.

Precision Antigen-APC Loading Matrix

Sophisticated loading protocols using tandem minigenes or peptide-pulsed DCs to maximize cross-presentation efficiency for coordinated CD4+ and CD8+ T cell responses.

TME-Remolding Synergistic Adjuvants

Leveraging bacterial adjuvants to normalize tumor vasculature and reprogram M1 macrophages, triggering CCL5-mediated recruitment for superior NRT infiltration.

Why Choose Creative Biolabs?

Comprehensive "Target-to-Asset" Solution

We go beyond simple prediction, providing actionable cell assets that are enriched, expanded, and functionally ranked for clinical-ready data packages.

Versatile NRT Source Strategy

Our platform supports parallel discovery from both peripheral blood (PBMC) and tumor-infiltrating lymphocytes (TILs), identifying low-frequency TCRs often missed by standard methods.

Persistence-Oriented TCR Discovery

We focus on identifying TCR clones that maintain functional "toughness" and resist exhaustion under repetitive tumor stimulation, not just initial peak killing.

End-to-End Preclinical Integrity

From NGS-based discovery to automated ex vivo manufacturing and rigorous QC, we ensure high-yield, high-viability cell products with full traceability.

Research Insight: Overcoming Solid Tumor Barriers via Synergistic ACT

Bacterial Adjuvants Remold the TME for Enhanced NRT Infiltration

The dense stroma and immunosuppressive milieu of solid tumors often impede the infiltration of adoptively transferred T cells. Groundbreaking research (Zhu et al., 2024) reveals that remolding the tumor microenvironment (TME) can significantly augment ACT efficacy.

TME Reprogramming: Intratumoral bacterial adjuvants normalize vasculature and shift macrophages towards the M1 phenotype, creating a T cell-favorable environment.
CCL5-Mediated Recruitment: Mature M1 macrophages produce abundant CCL5, which recruits CCR5+ neoantigen-activated T cells into the tumor core.
Dual Spatial Attack: This combination enables a potent synergy: bacteria target the inner core while NRTs attack the tumor periphery, achieving eradication in advanced models.

Schematic of CCL5 secretion and adoptive T cell recruitment via E. coli-mediated TAM reprogramming.

Fig.1 E. coli reprograms TAMs to secrete CCL5 and recruit adoptively transferred T cells.^1,2

Preclinical Development FAQs

While TILs are naturally enriched for tumor-reactive clones, they are often in a state of terminal exhaustion. PBMCs provide a source of "fresher" T cells with higher proliferative potential. Our parallel strategy allows you to capture high-affinity NRTs from the periphery that may not yet have infiltrated the tumor.

We utilize multi-marker flow cytometry and cytokine release assays (e.g., IFN-γ ELISpot) after restimulation with mutant versus wild-type peptides. This in vitro validation ensures that the T cells specifically recognize the neoepitope and do not react against the corresponding normal peptide.

Yes. We offer complete TCR cloning and lentiviral or retroviral transduction services to engineer both human and murine T cells. This is ideal for in vivo POC studies in syngeneic or humanized mouse models.

Ranking is based on a multi-dimensional score including antigen-specific killing efficiency, cytokine polyfunctionality, structural TCR affinity, and the avoidance of "exhaustion-prone" transcriptional signatures identified via cellular RNA-profiling.

Absolutely. We specialize in T cell-tumor organoid co-culture assays. This provides a more physiologically relevant in vitro model to evaluate NRT infiltration and killing within a dense 3D structure before moving to in vivo studies.