- |||||||||| Journal: Optimizing activation and culture conditions for the production of (Pubmed Central) - Nov 18, 2025
Using killing assays, we confirmed that these cytokine protocols improved the anti-tumour effects. These results will be useful for the development of CB-CAR-T/NK-cell therapies and suggest the potential of these modalities.
- |||||||||| RNDO-564 / Rondo Therap
Comprehensive Characterization of RNDO-564, a First-in-Class CD28 x Nectin-4 Bispecific Antibody for the Treatment of Solid Tumors (Poster Hall (Exhibit Halls AB); Virtual) - Oct 3, 2025 - Abstract #SITC2025SITC_1182;
Mechanistic data highlights its potential to restore T-cell function and overcome tumor antigen heterogeneity. A Phase 1, first-in-human, dose-escalation study in mUC and other Nectin-4-expressing tumors is ongoing.Ethics Approval Cynomolgus study was approved and designated an IACUC number D16-00594 (A4112-01).Abstract 889 Figure 1Request permissionsCostimulatory bispecific, RNDO-564, for immune primed tumors
- |||||||||| Izervay (avacincaptad pegol intravitreal solution) / Astellas, doxorubicin hydrochloride / Generic mfg., Macugen (pegaptanib) / Bausch Health
Review, Journal: Aptamers as therapeutic targets: prospects and progress in the treatment of cancers. (Pubmed Central) - Jun 7, 2025
Pegaptanib and Izervay are the approved aptamers against age-related macular degeneration (AMD) that target vascular endothelial growth factor (VEGF) and block complement component protein C5, respectively...Aptamosomes, encapsulating drugs like doxorubicin, effectively reduce tumour size and are highly advantageous over targeted drug delivery...It also outlines the roles of aptamers and connects their modes of action with specific cancer types. The content is highly detailed, providing a comprehensive understanding of aptamer therapy and its applications.
- |||||||||| Persistent elimination of tumors via balanced regulation of immune signals (Section 38; Poster Board No: 1) - Mar 25, 2025 - Abstract #AACR2025AACR_4424;
Pre-clinical toxicity and PK/PD studies in cynomolgus monkey have shown a promising safety and toxicity profile, with a dose up to 100mg/kg being tolerated. These encouraging results prompted us to advance JLM019 for clinical studies in humans.
- |||||||||| Undisclosed bispecific antibody / Rondo Therap
A novel CD28 x Nectin-4 costimulatory bispecific antibody for advanced bladder cancer. (Level 1, West Hall; Poster Bd #: G6) - Jan 7, 2025 - Abstract #ASCOGU2025ASCO_GU_281;
RNDO-564 has a high affinity Nectin-4 binding arm and an affinity-tuned CD28 arm optimized for activity in metastatic bladder cancer. A phase 1 study is planned to evaluate the safety, tolerability, PK/PD, and clinical activity of RNDO-564 alone and in combination with CPI in mUC.
- |||||||||| Undisclosed bispecific antibody / Rondo Therap
A novel CD28 x Nectin-4 costimulatory bispecific antibody targeting metastatic bladder cancer (Exhibit Halls AB - George R. Brown Convention Center) - Oct 4, 2024 - Abstract #SITC2024SITC_581;
Conclusions RNDO-564 has favorable functional and developability characteristics and is being developed to enter a Phase I clinical trial in 2025 targeting mUC. Ethics Approval The study was approved and designated an IACUC number ASP #: 980701.Download figure Open in new tab Download powerpoint Abstract 939 Figure 1 Schematic illustrating RNDO-564
- |||||||||| Trial completion date, Trial primary completion date: CYNEPSA: Cytokine Expression in Psoriasis Patients with and Without Joint Involvement (clinicaltrials.gov) - Sep 4, 2024
P=N/A, N=40, Recruiting,
Ethics Approval The study was approved and designated an IACUC number ASP #: 980701.Download figure Open in new tab Download powerpoint Abstract 939 Figure 1 Schematic illustrating RNDO-564 Trial completion date: Aug 2024 --> Aug 2026 | Trial primary completion date: Aug 2024 --> Aug 2026
- |||||||||| theralizumab (TAB08) / TheraMab
Discovery of agonist CD28-specific single domain antibodies from alpaca (Section 42) - Mar 5, 2024 - Abstract #AACR2024AACR_3799;
Development of superagonistic CD28-targeting antibody has been paused after TeGenero's TGN1412 Phase 1 trial in 2006 due to life-threatening cytokine release syndrome...All purified VHH-Fc showed sub-nanomolar affinity by ELISA and bind to primary T cells by flow cytometry. Three VHH-Fc induced IL-2 production in a primary T cells activation assay only when cross-linked and in the presence of CD3 co-stimulation and are suitable for further bispecific T cell engager development.
- |||||||||| Journal, IO biomarker: NKG2D receptor signaling shapes T cell thymic education. (Pubmed Central) - Nov 11, 2023
The data presented in this study indicate that NKG2D impacts thymic T cell development at a fundamental level by reducing the TCR threshold and affecting the functional imprint of the thymic progeny. In summary, understanding the impact of NKG2D on thymic T cell development and TCR signaling contributes to our knowledge of immune system regulation, immune dysregulation, and the design of immunotherapies.
- |||||||||| NI-3201 / Light Chain Biosci
NI-3201,a PD-L1xCD28 bispecific antibody for immune checkpoint-dependent CD28 co-stimulation (Section 24; Poster Board #20) - Mar 14, 2023 - Abstract #AACR2023AACR_5134;
The mechanism of action of NI-3201 and the data presented herein support the use of this molecule as a universal combination partner for CD3-bispecifics. Pre-clinical development of NI-3201 is ongoing, with pharmacokinetic and tolerability studies in non-human primates planned for early 2023.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen, Lunsumio (mosunetuzumab) / Roche, Biogen
EVOLVETM: A novel T cell engager platform with integrated CD2 costimulation engineered for the treatment of immune suppressive tumors (Section 24; Poster Board #18) - Mar 14, 2023 - Abstract #AACR2023AACR_5132;
Pre-clinical development of NI-3201 is ongoing, with pharmacokinetic and tolerability studies in non-human primates planned for early 2023. Bispecific antibodies which bind a tumor antigen and the CD3 heterodimer of the T cell receptor to form a synthetic immunological synapse represent a class of T cell engagers that has been clinically validated with the approvals of blinatumomab (Blinctyo
- |||||||||| Review, Journal, PD(L)-1 Biomarker, IO biomarker: Targeting Cbl-b in cancer immunotherapy. (Pubmed Central) - Feb 7, 2023
In translating Cbl-b inhibitors to clinic, we propose specific gene expression profiles that may identify patient populations most likely to benefit. Overall, novel Cbl-b inhibitors provide antigen-specific immune stimulation and are a promising therapeutic tool in the field of immuno-oncology.
- |||||||||| glofitamab (RG6026) / Roche
Phase 1 Study of CD19 Targeted CD28 Costimulatory Agonist in Combination with Glofitamab to Enhance T Cell Effector Function in Relapsed/Refractory B Cell Lymphoma (ENMCC - Hall D) - Nov 4, 2022 - Abstract #ASH2022ASH_2515;
P1
Across the different study parts, the treatment schedule is consistent with a single fixed dose of obinutuzumab (1000mg intravenously) given at least 3 days prior to glofitamab step up dosing (2.5/10/30mg)...Commencement of part 4, the expansion phase, including decision on the RO7443904 dose will be guided by a concerted review of safety, PK, and PD data from all dose escalation parts...Figure 1: Efficacy study in a disseminated DLBCL model in humanized NSG mice treated with monotherapy of glofitmab (0.15 mg/kg) or CD19-CD28 (1 mg/kg) as well as with a combination of both. The data suggest a strong anti-tumor effect when both agents are combined.
- |||||||||| A Bifunctional Tumor Activated Immunomodulator (TRACIr) Targeting PD-L1 And CD28 Is a Potent Enhancer of T Cell-Mediated Anti-Tumor Activity (Hall C) - Oct 6, 2022 - Abstract #SITC2022SITC_1630;
However, the first phase 1 clinical trial of the CD28 agonistic antibody TGN1412 failed due to an unexpected and rapid systemic proinflammatory cytokine response...PD-L1 blocking activity was comparable with atezolizumab, avelumab, nivolumab, and pembrolizumab...Finally, TRACIr was well tolerated in NHPs at high doses and exhibited half-life extended pharmacokinetics. Conclusions Preclinical activity and safety profiles of PDL1xCD28 TRACIr support its further development as an attractive bifunctional T cell modulator.
- |||||||||| theralizumab (TAB08) / TheraMab
A novel fully human CD28 antibody that cross-reacts with CTLA-4 and mouse CD28 for potential applications in cancer immunotherapy (Hall C) - Oct 6, 2022 - Abstract #SITC2022SITC_1382;
Conclusions VE19ZH is a promising module for cancer immunotherapy with unique properties: (i) Fully human mAb for minimal immunogenicity (ii) Potent co-stimulator for full T cell activation (iii) Conventional agonist of CD28 and not super-agonistic like TGN1412 (iv) cross reacts with mouse CD28 for better assessment in immunocompetent mouse models (v) Binds to human CTLA-4 for potential checkpoint inhibition. The potential of VE19ZH to boost T cell response via CD28 activation and CTLA-4 blockade is currently being investigated in vitro and in vivo.
- |||||||||| Journal: Plasmid-Based Donor Templates for Nonviral CRISPR/Cas9-Mediated Gene Knock-In in Human T Cells. (Pubmed Central) - Sep 29, 2022
© 2022 Wiley Periodicals LLC. Basic Protocol 1: Purification of human CD4 or CD8 T cells from blood Basic Protocol 2: Activation of purified CD4 or CD8 T cells using TransAct CD3/CD28 agonist-conjugated nanomatrix Basic Protocol 3: Preparation of Cas9/sgRNA RNPs Basic Protocol 4: Transfection of CAS9-RNP and knock-in template into human T cells Support Protocol 1: Purity check following magnetic T cell isolation Support Protocol 2: Dextramer staining of TCR-edited T cells Support Protocol 3: Functional characterization of TCR knock-in T cells Support Protocol 4: Detection of knock-in reporter activity in CRISPR/CAS9-edited T cells
- |||||||||| Trial completion date, Trial initiation date, Trial primary completion date: CYNEPSA: Cytokine Expression in Psoriasis Patients with and Without Joint Involvement (clinicaltrials.gov) - Aug 4, 2022
P=N/A, N=40, Not yet recruiting,
Basic Protocol 1: Purification of human CD4 or CD8 T cells from blood Basic Protocol 2: Activation of purified CD4 or CD8 T cells using TransAct CD3/CD28 agonist-conjugated nanomatrix Basic Protocol 3: Preparation of Cas9/sgRNA RNPs Basic Protocol 4: Transfection of CAS9-RNP and knock-in template into human T cells Support Protocol 1: Purity check following magnetic T cell isolation Support Protocol 2: Dextramer staining of TCR-edited T cells Support Protocol 3: Functional characterization of TCR knock-in T cells Support Protocol 4: Detection of knock-in reporter activity in CRISPR/CAS9-edited T cells Trial completion date: May 2024 --> Aug 2024 | Initiation date: May 2022 --> Aug 2022 | Trial primary completion date: May 2024 --> Aug 2024
- |||||||||| ifosfamide / Generic mfg., zoledronic acid / Generic mfg., doxorubicin hydrochloride / Generic mfg.
Preclinical, Journal: Therapeutic Potential of Ex Vivo Expanded γδ T Cells against Osteosarcoma Cells. (Pubmed Central) - Jul 29, 2022
The expanded γδ T cells were isolated by magnetic cell separation or fluorescence-activated cell sorting, cultured with two OS cell lines (KHOS/NP and MG-63) at various cell ratios with or without doxorubicin or ifosfamide, and analyzed for cytotoxicity and cytokine secretion...The expanded γδ T cells exhibited potent in vitro cytotoxicity against OS in a ratio- and time-dependent manner. The γδ T cells may enhance the effect of chemotherapeutic agents against OS and may be a new treatment strategy, including chemo-immunotherapy, for OS.
- |||||||||| ERY-974 / Roche
P1 data, Journal: Determination of starting dose of the T cell-redirecting bispecific antibody ERY974 targeting glypican-3 in first-in-human clinical trial. (Pubmed Central) - Jul 23, 2022
P1
For the phase I clinical trial, we selected 3.0 ng/kg as a starting dose, which was lower than the first-in-human dose calculated from both the no observed adverse effect level and minimal anticipated biological effect level. Combining these two methods to determine the first-in-human dose of strong immune modulators such as T cell-redirecting antibodies would be a suitable approach from safety and efficacy perspectives.Clinical trial registration: JapicCTI-194805/NCT05022927.
- |||||||||| Biomarker, Journal, Tumor microenvironment: Nicotinamide drives T cell activation in the mammary tumor microenvironment. (Pubmed Central) - Jun 8, 2022
Here, we demonstrate that T cells infiltrating mouse mammary carcinomas that are therapeutically controlled by NAM also express multiple markers of late-stage activation. Taken together, these findings lend additional support to the notion that the antineoplastic effects of NAM involve at least some degree of restored cancer immunosurveillance.
- |||||||||| theralizumab (TAB08) / TheraMab
A humanized mouse model to evaluate the systemic adverse effects of cytokine release syndrome induced by immunoactivating drugs () - May 9, 2022 - Abstract #CIMT2022CIMT_238;
The lack of predictive preclinical models to evaluate antibodymediated adverse effects can lead to clinical failures, such as TGN1412, a humanized anti-CD28 monoclonal antibody that caused life-threatening cytokine release syndrome (CRS) during the firstin-man trial...We have demonstrated that the novel mouse model using PBMC-humanized NSG™ or derivative strains can successfully detect CRS induced by immunoactivating antibodies in a dose- and timedependent manner. Our data support that the PBMC humanized mouse model for CRS assessment is a valuable tool to assess in vivo safety of experimental human immunoregulatory therapies, including immune checkpoint inhibitors, CAR T, and bispecific antibodies.
- |||||||||| davoceticept (ALPN-202) / Alpine Immune Sci
Dose escalation of davoceticept, a conditional CD28 costimulator and dual checkpoint inhibitor, in advanced malignancies (NEON-1). (Available On Demand; 215) - Apr 28, 2022 - Abstract #ASCO2022ASCO_1620;
P1
These findings support an additive benefit of combining CD28 agonism with checkpoint inhibition and identify biologically active dose regimens of davoceticept for subsequent single agent development, and provide further rationale for combination study. Expansion cohorts, including cutaneous melanoma and PD-L1-positive cancers, are planned, and a combination study with pembrolizumab has initiated (NCT04920383).
- |||||||||| Optimized CD28 bispecific antibodies for targeted activation of T cells within the tumor microenvironment (Section 37) - Mar 9, 2022 - Abstract #AACR2022AACR_4815;
The resulting TAA-CD28 κλ bodies can enhance the antitumor response induced by CD3-retargeting bsAbs via the induction of T cell proliferation and activation, increased cytokine secretion and boosted anti-tumoral cytotoxicity. Other anti-TAA arms are being explored, to expand the panel of TAAs that could be easily paired with our anti-CD28 platform arms.
- |||||||||| ALPN-202 / Alpine Immune Sci
Development of a clinical ex vivo assay for the assessment of therapeutic CD28 costimulatory pathway engagement (Poster Hall) - Oct 1, 2021 - Abstract #SITC2021SITC_231;
P1
This assay has been successfully employed to monitor controlled CD28 costimulation by the CD28 agonist therapeutic candidate ALPN-202, helping to establish a PK/PD relationship that is consistent with preclinical data. More broadly, this type of cell-based, ex vivo TDC assay could be adapted to assess costimulatory receptor engagement, particularly target-dependent costimulation, for other therapeutic agonists in clinical development.
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