Liposomal phytohemagglutinin: In vivo T‐cell activator as a novel pan‐cancer immunotherapy

T-cell recognition of somatic mutation-derived cancer neoepitopes can lead to tumor regression. Due to the difficulty to identify effective neoepitopes, constructing a database for sharing experimentally validated cancer neoantigens will be beneficial to precise cancer immunotherapy. Meanwhile, the routine neoepitope prediction in silico is important but laborious for clinical use. Here we present NEPdb, a database that contains more than 17,000 validated human immunogenic neoantigens and ineffective neoepitopes within human leukocyte antigens (HLAs) via curating published literature with our semi-automatic pipeline. Furthermore, NEPdb also provides pan-cancer level predicted HLA-I neoepitopes derived from 16,745 shared cancer somatic mutations, using state-of-the-art predictors. With a well-designed search engine and visualization modes, this database would enhance the efficiency of neoantigen-based cancer studies and treatments. NEPdb is freely available at http://nep.whu.edu.cn/.

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Reinforcement of Cancer Immunotherapy by Adoptive Transfer of Cblb-Deficient Cytotoxic T Lymphocytes Combined with a Dendritic Cell Vaccine

Blood ◽

10.1182/blood.v116.21.957.957 ◽

2010 ◽

Vol 116 (21) ◽

pp. 957-957

Author(s):

Christina Lutz-Nicoladoni ◽

Patrizia Stoizner ◽

Magdalena Pircher ◽

Stephanie Wallner ◽

Anna Maria Wolf ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Dendritic Cell ◽

Cancer Immunotherapy ◽

Cytotoxic T Lymphocytes ◽

Adoptive Transfer ◽

Ex Vivo ◽

Dc Vaccine

Abstract Abstract 957 Introduction: Various approaches to induce immunological rejection of tumors including transfer of autologous tumor infiltrating lymhocytes (TIL) after ex vivo clonal expansion or application of ex vivo transduced antigen specific T cell (TCR) transgenic T cells have been elaborated. In general, adoptive T cell transfer (ATC) has been combined with lympho-depleting agents (e.g. cyclophosphamide). However, the therapeutic efficacy of these cancer immunotherapy approaches is limited due to insufficient in vivo activation, expansion and survival of transferred effector immune cells, which is mainly due to suppressive mileu signals and immune evasion mechanisms induced by TGF-β. The E3 ubiquitin ligase Cbl-b is a key regulator of T cell activation and is assumed to confer TGF-β resistance. Thus we performed a proof-of-concept study evaluating Cbl-b targeting as “intracellular adjuvant” strategy to improve ATC for cancer immunotherapy. Material and Methods: We first tested the in vitro sensitivity of CTL towards TGF-β mediated immuno-suppressive cues and then in vivo evaluated the anti-tumor reactivity of cblb-deficient cytotoxic T lymphocytes (CTL) in murine tumor models alone or in combination with a dendritic cell (DC) vaccine. Results: Cblb-deficient CTL are hyper-responsive to TCR/CD28-stimulation in vitro and protected from the negative cues induced by TGF-β as determined by quantification fo IFN-g secretion and quantification of their proliferative capacity. Unexpectedly, adoptive transfer of polyclonal, non TCR-transgenic cblb-deficient CD8+ CTL, however, is not sufficient to reject B16ova or EG7 tumors in vivo, which is in clear contrast to previous reports using lymphopenic animals receiving adoptively transferred TCR-transgenic T cells. Thus, we next evaluated in vivo re-activation of adoptively transferred cblb-deficient T cells by a DC vaccine (i.e. SIINFEKL-pulsed DC). In strict contrast to ATC monotherapy, this approach now markedly delays tumor outgrowth and significantly increase survival rates, which is paralleled by an increased CTL infiltration rate to the tumor site and an enrichment of ova-specific and IFN-g-secreting CTL in the draining lymph nodes. Moreover, compared to wild-type CTL, cblb-deficient mice vaccinated with the DC vaccine show an increased cytolytic activity in vivo. Conclusions: In summary, we provide experimental evidence that genetic inactivation of cblb in polyclonal, non-TCR transgenic adoptively transferred CTL might serve as a novel “adjuvant approach”, suitable to augment the effectiveness of anti-cancer immunotherapies using ATC in immune-competent recipients. Disclosures: No relevant conflicts of interest to declare.

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In Vitro and in Vivo Imaging of Initial T-B Cell Interactions in the Setting of B Cell-Based Cancer Immunotherapy

Blood ◽

10.1182/blood.v124.21.2740.2740 ◽

2014 ◽

Vol 124 (21) ◽

pp. 2740-2740

Author(s):

Kerstin Wennhold ◽

Nela Klein-Gonzalez ◽

Michael von Bergwelt-Baildon ◽

Alexander Shimabukuro-Vornhagen

Keyword(s):

T Cells ◽

T Cell ◽

B Cells ◽

B Cell ◽

Cancer Immunotherapy ◽

Cell Interactions ◽

Migration Behavior ◽

Cell Zone

Abstract In recent years, there has been a growing interest in the use of B cells for cellular immunotherapy, since B cell-based cancer vaccines have yielded promising results in preclinical animal models. Contrary to dendritic cells (DCs), we know little about the migration behavior of B cells in vivo. Therefore, we investigated the interactions between CD40-activated (CD40) B cells and cytotoxic T cells in vitro and the migration behavior of CD40B cells in vivo. The dynamic interactions of human antigen-presenting cells and antigen-specific T cells were observed by time-lapse videomicroscopy. The migratory and chemoattractant potential of CD40B cells was analyzed by flow cytometry and standard transwell migration assays. GFP+ CD40B cells or CD40B cells isolated from Luciferase+mice were used for subsequent in vivo studies. Murine CD40B cells show similar migratory and chemotactic characteristics compared to human CD40B cells. Upon CD40-activation, B cells upregulate the important molecules involved in lymh node homing (CD62L, CCR7/CDCR4), which are functional and induce chemotaxis of T cells in vitro. Striking differences were observed for interactions of human CD40B cells or DCs with T cells. Antigen-loaded CD40B cells differ from immature and mature DCs by displaying a rapid migratory pattern undergoing highly dynamic, short-lived (7.5 min) and sequential interactions with cognate T cells. In vivo, CD40B cells migrate to the spleen and the lymph nodes, where they enrich in the B cell zone before traveling to B cell/ T cell boundary close to the T cell zone. CD40B cell interactions with T cells are dynamic and short-lived and thereby differ from DCs. Taken together, the migration behavior of CD40B cells and their interaction with T cells underline their potential as cellular adjuvant for cancer immunotherapy. Disclosures No relevant conflicts of interest to declare.

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Repositioning Azelnidipine as a Dual Inhibitor Targeting CD47/SIRPα and TIGIT/PVR Pathways for Cancer Immuno-Therapy

Biomolecules ◽

10.3390/biom11050706 ◽

2021 ◽

Vol 11 (5) ◽

pp. 706

Author(s):

Xiuman Zhou ◽

Ling Jiao ◽

Yuzhen Qian ◽

Qingyu Dong ◽

Yixuan Sun ◽

...

Keyword(s):

T Cell ◽

Cancer Immunotherapy ◽

Cd8 T Cell ◽

Dependent Manner ◽

Dual Inhibitor ◽

Macrophage Phagocytosis ◽

Hypertensive Drug ◽

And Function

Strategies boosting both innate and adaptive immunity have great application prospects in cancer immunotherapy. Antibodies dual blocking the innate checkpoint CD47 and adaptive checkpoint PD-L1 or TIGIT could achieve durable anti-tumor effects. However, a small molecule dual blockade of CD47/SIRPα and TIGIT/PVR pathways has not been investigated. Here, an elevated expression of CD47 and PVR was observed in tumor tissues and cell lines analyzed with the GEO datasets and by flow cytometry, respectively. Compounds approved by the FDA were screened with the software MOE by docking to the potential binding pockets of SIRPα and PVR identified with the corresponding structural analysis. The candidate compounds were screened by blocking and MST binding assays. Azelnidipine was found to dual block CD47/SIRPα and TIGIT/PVR pathways by co-targeting SIRPα and PVR. In vitro, azelnidipine could enhance the macrophage phagocytosis when co-cultured with tumor cells. In vivo, azelnidipine alone or combined with irradiation could significantly inhibit the growth of MC38 tumors. Azelnidipine also significantly inhibits the growth of CT26 tumors, by enhancing the infiltration and function of CD8+ T cell in tumor and systematic immune response in the tumor-draining lymph node and spleen in a CD8+ T cell dependent manner. Our research suggests that the anti-hypertensive drug azelnidipine could be repositioned for cancer immunotherapy.

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Cold Plasma with Immunomodulatory Properties Has Significant Anti-Lymphoma Activities in Vitro and In Vivo

Blood ◽

10.1182/blood-2019-131065 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5307-5307 ◽

Cited By ~ 1

Author(s):

Fengdong Cheng ◽

Dayun Yan ◽

Jie Chen ◽

Michael Keidar ◽

Eduardo Sotomayor

Keyword(s):

T Cells ◽

T Cell ◽

Cancer Immunotherapy ◽

Cd4 T Cells ◽

Antitumor Effects ◽

Helium Gas ◽

Gas Control ◽

First Time

In recent years, cancer immunotherapy has revolutionized cancer care. Remarkable clinical efficacy and durable responses to checkpoint blockade antibodies or to genetically engineered T-cells (CAR T cell) have been observed in patients with multiple cancers. However, not all cancer patients benefit from these therapies and as such novel immunotherapeutic approaches are needed. The cold atmospheric plasma (CAP) is a form of near room temperature ionized gas, which has shown a promising application in cancer therapy given its antitumor effects in vitro as well as in vivo. For the first time, we have shown that upon CAP treatment, the viability of the immune cells remained unaffected. Strikingly, we observed a significantly stronger immune activation of those CAP treated cells when compare with helium gas control. First, we have demonstrated that even without LPS stimulation, in vitro exposure of peritoneal elicited macrophages (PEM) to CAP for 15 or 30 seconds was sufficient to trigger the production of the pro-inflammatory cytokines IL-12 and IL-6. In addition, decreased production of anti-inflammatory cytokine IL-10 and diminished the expression of PD-L1 were observed in CAP-treated PEM as well. It indicated that CAP treatment may potentially facilitate PEMs as better activator of T cells. Second, in lieu of the stimulatory effects of CAP upon PEM, we asked whether CAP could enhance T-cell activation. So we isolated T cells from spleens of C57BL/6 mice and exposed these T cells to CAP followed by anti-CD3/CD28 stimulation. Our study shown that the production of IL-2 and IFN-g were significantly increased by T-cells treated with CAP as compared with helium gas control. Furthermore, to gain insights into effects of CAP upon immune responses in vivo, we isolated lymph nodes from OTII mice and directly exposed these LNs with CAP, helium gas control or left untreated. Then CD4+ T cells were further isolated from the LNs and cultured with macrophages in the presence or absence of OVA peptide for 48 hours, respectively. Surprisingly, CD4+ T cells isolated from CAP-treated LNs displayed enhanced function indicated by its increased production of IL-2 and IFN-g. More importantly, strong in vivo anti-tumor effects were observed when adoptively transfer CAP exposed T cells to lymphoma bearing animals. Taken together, we have shown for the first time an elevated immune-stimulatory effect of CAP upon both APCs and T cells in vitro and in vivo. Our finding may potentially shed light of a novel therapeutic approach for future cancer immunotherapy. Disclosures No relevant conflicts of interest to declare.

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Blockade of CTLA-4 on both effector and regulatory T cell compartments contributes to the antitumor activity of anti–CTLA-4 antibodies

Journal of Experimental Medicine ◽

10.1084/jem.20082492 ◽

2009 ◽

Vol 206 (8) ◽

pp. 1717-1725 ◽

Cited By ~ 565

Author(s):

Karl S. Peggs ◽

Sergio A. Quezada ◽

Cynthia A. Chambers ◽

Alan J. Korman ◽

James P. Allison

Keyword(s):

T Cell ◽

Antitumor Activity ◽

Immune Responses ◽

Cancer Immunotherapy ◽

Regulatory T Cell ◽

Negative Regulator ◽

Therapeutic Effects ◽

Cell Compartment ◽

Genetic Ablation

Cytotoxic T lymphocyte–associated antigen 4 (CTLA-4) is a critical negative regulator of immune responses. Uniquely among known inhibitory receptors, its genetic ablation results in a fulminating and fatal lymphoproliferative disorder. This central regulatory role led to the development of antibodies designed to block CTLA-4 activity in vivo, aiming to enhance immune responses against cancer. Despite their preclinical efficacy and promising clinical activity against late stage metastatic melanoma, the critical cellular targets for their activity remains unclear. In particular, debate has focused on whether the effector T cell (Teff) or regulatory T cell (T reg cell) compartment is the primary target of antibody-mediated blockade. We developed a mouse expressing human instead of mouse CTLA-4, allowing us to evaluate the independent contributions of CTLA-4 blockade of each T cell compartment during cancer immunotherapy in an in vivo model of mouse melanoma. The data show that although blockade on effector cells significantly improves tumor protection, unicompartmental blockade on regulatory cells completely fails to enhance antitumor responses. However, concomitant blockade of both compartments leads to a synergistic effect and maximal antitumor activity. We conclude that the combination of direct enhancement of Teff cell function and concomitant inhibition of T reg cell activity through blockade of CTLA-4 on both cell types is essential for mediating the full therapeutic effects of anti–CTLA-4 antibodies during cancer immunotherapy.

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THE APPLICATION FOR CANCER IMMUNOTHERAPY USING in vivo OR in vitro ACTIVATED γδ T CELL

Japanese Journal of Transfusion and Cell Therapy ◽

10.3925/jjtc.62.3 ◽

2016 ◽

Vol 62 (1) ◽

pp. 3-12

Author(s):

Hirohito Kobayashi ◽

Hitoshi Kanno

Keyword(s):

T Cell ◽

Cancer Immunotherapy ◽

Γδ T Cell

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Varicella-Zoster-Virus-Specific CD4+ Cytotoxic T Cells as Tumor-Specific Effector Cells in Cancer Immunotherapy.

Blood ◽

10.1182/blood.v106.11.1292.1292 ◽

2005 ◽

Vol 106 (11) ◽

pp. 1292-1292

Author(s):

Silke Landmeier ◽

Sibylle Pscherer ◽

Bodo Eing ◽

Cliona M. Rooney ◽

Heribert Juergens ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Varicella Zoster Virus ◽

Cancer Immunotherapy ◽

Peripheral Blood ◽

Cytotoxic T Cell ◽

Dependent Manner ◽

Varicella Zoster ◽

Ifn Γ

Abstract Adoptive transfer of gene-engineered T cells expressing tumor antigen-specific chimeric receptors (chRec) is a promising tool in cancer immunotherapy. A major limitation is the failure of chRec to induce proliferative T cell responses, resulting in a rapid loss of function. To provide a strategy for reexpansion of tumor-reactive T cells in vivo, we generated dual-specific T cells that respond to varicella zoster virus while also possessing chRec-mediated tumor reactivity. We expanded VZV-specific cytotoxic T cell lines (VZV-CTL) from four seropositive donors by culturing peripheral blood-derived T cells with lysates extracted from VZV-infected fibroblasts. Repeated stimulation with VZV lysates resulted in efficient and continued expansion for 10–12 weeks. >1x109 T cells were routinely obtained from a starting number of 1x106 peripheral blood T cells. The T cells displayed a mainly CD3+CD4+ (90±5%) phenotype. ELISPOT assays showed specific, MHC class II-restricted IFN-γ release in response to CD40-activated B cells expressing the viral glycoproteins gE and IE62. VZV-CTL belong to a non-regulatory effector T cell subset, shown by their failure to exert antiproliferative effects against cocultured autologous T cells and lack of Foxp3 expression. Retroviral transduction with chRec recognizing the tumor ganglioside antigen GD2 (14.G2a-ζ) and the B cell lineage antigen CD19 (CD19-ζ) resulted in receptor surface expression on 29–74% and 39–45% of cells, respectively. Gene-modified VZV-CTL efficiently recognized antigen-expressing tumor targets in an MHC-independent manner, as demonstrated by antigen-specific secretion of IFN-γ in response to coincubation with GD2-expressing tumor targets. Furthermore, chRec-transduced VZV-CTL performed potent and antigen-specific tumor cytolysis. Antibody blocking experiments revealed that tumor cells were lysed in a granulysin-dependent manner. ChRec-transduced CD3+CD4+ cytolytic VZV-CTL may provide a source of highly potent tumor-reactive cells for adoptive immunotherapy cancer. Endogenous viral reactivations or administration of booster doses of varicella vaccine may lead to survival of these tumor-reactive T cells for prolonged periods of time in vivo.

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442 ICT01, an anti-BTN3A mAb that activates Vg9Vd2 T cells, plus interleukin-2: a potent and promising combination for cancer immunotherapy

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-sitc2020.0442 ◽

2020 ◽

Vol 8 (Suppl 3) ◽

pp. A468-A468

Author(s):

Aude de Gassart ◽

Patrick Brune ◽

LE Suong ◽

Sophie Agaugué ◽

Emmanuel Valentin ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Cancer Immunotherapy ◽

T Cell Activation ◽

Immune Cells ◽

Cell Activation ◽

Human Pbmcs ◽

Vγ2vδ2 T Cells

Background gdT-cells are attractive targets for cancer immunotherapy given their strong cytolytic and pro-inflammatory cytokine secretion activities, and the association between tumor infiltration and positive prognosis.1 2 ImCheck Therapeutics is developing ICT01, an anti-human butyrophilin-3A (BTN3A/CD277) mAb specifically activating g9d2 T-cells in a phosphoantigen (pAg)-independent manner. ICT01 is currently in a Phase 1/2a study in solid and hematologic tumors (NCT04243499).IL-2 has been shown to expand g9d2 T-cells in vitro and in non-human primates in presence of pAgs.3 4 5 We wanted to characterize the proliferative effects of combining ICT01 with IL-2 on γ9δ2 T-cells as an approach to potentiate g9d2 T-cell mediated cancer immunotherapy.Methods g9d2 T-cell activation and expansion was assessed in vitro in human PBMCs treated with ICT01±IL-2, and in vivo, in the blood of immunocompromised NCG mice engrafted with 20 × 106 human PBMCs and treated with ICT01 (single IV dose, 5 mg/kg on Day 1) ±IL-2 (0.3MIU/kg IP on Day 1–4). A dose-ranging ICT01 (single IV dose, 1 or 5 mg/kg on Day 1)+IL-2 combination (1 MIU SC QD on Days 1–5) study was conducted in cynomolgus monkeys.ResultsIn PBMCs cultures in vitro, ICT01 selectively activated g9d2 T-cells and IL-2 significantly enhanced ICT01-mediated g9d2 T-cell proliferation, this compartment reaching >50% of T-cells after 8 days of treatment versus ~10% with ICT01 alone. This was confirmed in vivo in mice models. Flow cytometry analysis of mice blood revealed a 5.5-fold increase in human g9d2 T-cell number in the combination groups compared to ICT01 or IL-2 alone treated animals, with g9d2 T-cell frequency reaching ~35% of the CD3+ T-cell compartment. In Cynomolgus, a specific expansion and activation of peripheral g9d2 T-cells from ~1–2% at baseline to up to 30% of T cells 7 days post ICT01 administration was observed. No ICT01 effect was observed on other immune cells. Histopathological examinations revealed a trend towards higher numbers of g9d2 T-cells in several organs in ICT01+IL-2 treated monkeys. There was no evidence for a systemic cytokine release syndrome at any time point. Adverse effects with variable severity were observed, most of them being reversible and commonly associated with IL-2 alone, and not reported in the IND-enabling GLP toxicity study with ICT01 monotherapy at doses up to 100 mg/kg.ConclusionsThese results demonstrate the ability of ICT01+IL-2 combination to trigger profound γ9δ2 T-cell activation and expansion, suggesting that the clinical combination of ICT01 with a lymphoproliferative cytokine (e.g., IL-2) may be a novel therapeutic approach for cancer patients.Ethics ApprovalPseudonymized samples isolated from healthy volunteers: whole blood by ImCheck Therapeutics under the agreement n° 7173 between ImCheck Therapeutic SAS and EFS PACA (Etablissement Français du Sang Provence-Alpes-cote d’Azur)ReferencesGentles AJ, Newman AM, Liu CL, et al. The prognostic landscape of genes and infiltrating immune cells across human cancers. Nature Medicine 2015;21(8):938–945.Tosolini M, Pont F, Poupot M, et al. Assessment of tumor-infiltrating TCRVγ9Vδ2 γδ lymphocyte abundance by deconvolution of human cancers microarrays. OncoImmunology 2017;6(3):e1284723.Nada MH, Wang H, Workalemahu G, Tanaka Y, Morita CT. Enhancing adoptive cancer immunotherapy with Vγ2Vδ2 T cells through pulse zoledronate stimulation. Journal for ImmunoTherapy of Cancer 2017;5(1):9.Sicard H, Ingoure S, Luciani B, et al. In Vivo Immunomanipulation of Vγ9Vδ2 T cells with a synthetic phosphoantigen in a preclinical nonhuman primate model. The Journal of Immunology 2005;175(8):5471–5480.Ali Z, Shao L, Halliday L, et al. Prolonged (E)-4-Hydroxy-3-Methyl-But-2-Enyl pyrophosphate-driven antimicrobial and cytotoxic responses of pulmonary and systemic Vγ2Vδ2 T cells in macaques. The Journal of Immunology 2007;179(12):8287–8296.

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P857 ONM-500 – a novel STING-activating therapeutic nanovaccine platform for cancer immunotherapy

Journal for ImmunoTherapy of Cancer ◽

10.1136/lba2019.11 ◽

2020 ◽

Vol 8 (Suppl 1) ◽

pp. A7-A8

Author(s):

Jason Miller ◽

Min Luo ◽

Hua Wang ◽

Zhaohui Wang ◽

Xinliang Ding ◽

...

Keyword(s):

T Cell ◽

Cancer Immunotherapy ◽

T Cell Activation ◽

Cell Activation ◽

Subcutaneous Administration ◽

Full Length ◽

Tumor Models ◽

Hpv16 E6 ◽

E6 And E7

BackgroundEfficacy of cancer vaccines requires the induction of tumor antigen-specific cytotoxic T-lymphocytes (CTL) to effectively clear established tumors. Orchestration of antigen presentation, co-stimulatory signaling, and innate cytokine signals are necessary steps for tumor-specific T-cell activation. The ONM-500 nanovaccine platform1-2 utilizes a novel pH-sensitive polymer that forms an antigen-encapsulating nanoparticle and functions both as a carrier for antigen delivery of both peptide and protein antigens to dendritic cells and acts as an adjuvant, activating the stimulator on interferon genes (STING) pathway and generating a CD8+ CTL response. Peptide antigens have translational challenges due to complex formulations and/or HLA-type-specific antigen sequence recognition, processing and presentation. Full-length protein antigens alleviate HLA subtype limitation, allowing coverage of multi-immunogenic T cell epitopes in patients. Pairing ONM-500 adjuvant with the full-length E6 and E7 oncoproteins from human papillomavirus (HPV) cancers shows great potential to treat HPV-associated cancer in patients.MethodsBased on the previously demonstrated STING-dependent T cell activation by ONM-500 [1], the nanovaccine was formulated with full-length HPV16 E6 and E7 proteins (recombinant), and the nanoparticle properties and antigen loading were characterized. In vivo lymph node accumulation following subcutaneous administration was evaluated using fluorescent nanovaccines. Direct binding of ONM-500 to recombinant human STING (CTD) was evaluated using isothermal titration calorimetry (ITC) compared to the endogenous ligand 2’,3’-cGAMP. Antitumor efficacy was evaluated in multiple syngeneic tumor models, including the TC-1 model which overexpresses HPV16 E6 and E7 with the ONM-500 vaccine in combination with anti-PD-1 checkpoint inhibitor. Long-term anti-tumor memory was evaluated in a follow-up rechallenge study after 60 days in tumor-free animals.ResultsCharacterization of ONM-500 nanovaccine shows reproducible particle chemi-physical properties and antigen loading. The nanoparticle size substantiates the effective lymph node accumulation for antigen cross-presentation in dendritic cells following subcutaneous administration. ITC studies with human STING demonstrated effective binding by ONM-500 adjuvant. The nanovaccine anti-tumor efficacy was previously demonstrated in melanoma, colorectal, and HPV-associated syngeneic tumor models. In TC-1 tumors, ONM-500 nanovaccine containing full-length E6/E7 protein showed 100% overall survival at 55 days (figure 1). Tumor growth inhibition was also improved over E7 antigen peptide formulated nanovaccine. A rechallenge study demonstrated long-term antigen-specific anti-tumor memory response.Abstract P857 Figure 1ConclusionsONM-500 STING-activating nanovaccines effectively deliver antigens in vivo to lymph nodes to elicit antigen-specific CTL response. The anti-tumor efficacy in multiple tumor models demonstrates the potential of ONM-500 as a general STING agonist cancer vaccine platform, and full-length E6/E7 incorporated ONM-500 is being developed for HPV-associated cancers.Ethics ApprovalAll animal procedures were performed with ethical compliance and approval by the Institutional Animal Care and Use Committee of the University of Texas Southwestern Medical Center (Protocol No. 2017-101954) and Pennsylvania State College of Medicine (Protocol No. 47682).ReferencesLuo M, Wang H, Wang Z, Cai H, Lu Z, Li Y, Du M, Huang G, Wang C, Chen X, Porembka MR, Lea J, Frankel AE, Fu YX, Chen ZJ, Gao J. A STING-activating nanovaccine for cancer immunotherapy. Nat Nanotechnol 2017; 12:648–654.Luo M, Liu Z, Zhang X, Han C, Samandi LZ, Dong C, Sumer BD, Lea J, Fu YX, Gao J. Synergistic STING activation by PC7A nanovaccine and ionizing radiation improves cancer immunotherapy. J Control Release 2019; 28:154–160.

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