- |||||||||| gamitrinib / Fox Chase Cancer Center, The Wistar Institute
Biomarker, Journal, PD(L)-1 Biomarker, IO biomarker: Integrated analyses of multi-omic data derived from paired primary lung cancer and brain metastasis reveal the metabolic vulnerability as a novel therapeutic target. (Pubmed Central) - Nov 27, 2024
The COVID-19 DNA vaccine INO-4800 at two doses (1.0?mg or 2.0?mg) showed an acceptable safety profile and modest immunogenicity, with the high-dose slightly more immunogenic than the low-dose.Clinical Trials Registration: www.chictr.org.cn, identifier is ChiCTR2000040146. In conclusion, our findings not only provide comprehensive and integrated perspectives of molecular underpinnings of LC-BrMs but also contribute to the development of a potential, rationale-based combinatorial therapeutic strategy with the goal of translating it into clinical trials for patients with LC-BrMs.
- |||||||||| VK-2019 / The Wistar Institute, Stanford University
Enrollment change, Trial completion date, Trial primary completion date: Clinical Trial of a Novel Small Molecule EBNA1 Inhibitor, VK 2019, in Patients With Epstein Barr Virus (EBV)-Positive Nasopharyngeal Cancer (NPC) and Other Epstein-Barr Virus (EBV)-Associated Cancers, With Pharmacokinetic and Pharmacodynamic Correlative Studies (clinicaltrials.gov) - Nov 4, 2024
P2, N=61, Recruiting,
In conclusion, our findings not only provide comprehensive and integrated perspectives of molecular underpinnings of LC-BrMs but also contribute to the development of a potential, rationale-based combinatorial therapeutic strategy with the goal of translating it into clinical trials for patients with LC-BrMs. N=30 --> 61 | Trial completion date: Feb 2026 --> Feb 2031 | Trial primary completion date: Feb 2025 --> Feb 2028
- |||||||||| Clinical, Journal, Head-to-Head: A head-to-head comparison of humoral and cellular immune responses of five COVID-19 vaccines in adults in China. (Pubmed Central) - Sep 5, 2024
Here, SARS-CoV 2-specific immune responses to DNA vaccine (INO-4800), mRNA vaccine (BNT162b2), Adenovirus-vectored vaccine (CONVIDECIA), Protein subunit vaccine (Recombinant COVID- 19 Vaccine (Sf9 Cells)), Inactivated Vaccine (KCONVAC) were examined longitudinally in healthy adults between Jan 15, 2021 and July 5, 2021 for 6 months...BNT162b2 (mRNA vaccine) exhibits the highest antibody levels among the five vaccines evaluated, regardless of whether the target is the wild-type virus or its variants. However, its cellular immune response may be weaker compared to CONVIDECIA (adenovirus type 5 vector vaccine).
- |||||||||| AZD8076 / AstraZeneca, Inovio, AZD5396 / Inovio, AstraZeneca
Enrollment closed: dMAbs for Prevention of COVID-19 (clinicaltrials.gov) - Jul 3, 2024
P1, N=61, Active, not recruiting,
However, its cellular immune response may be weaker compared to CONVIDECIA (adenovirus type 5 vector vaccine). Recruiting --> Active, not recruiting
- |||||||||| gamitrinib / Fox Chase Cancer Center, The Wistar Institute
Role of the inner mitochondrial membrane protein (Mic60) in MAPKi-resistant melanoma (Section 24) - Mar 5, 2024 - Abstract #AACR2024AACR_8064;
Mic60 is heterogeneously expressed and often reduced in melanoma. Although this is associated with increased cell invasion and metastatic propensity, the combination of Gamitrinib plus MAPKi restored mitochondrial cell death in therapy-resistant, Mic60-low melanoma cells.
- |||||||||| gamitrinib / Fox Chase Cancer Center, The Wistar Institute
Review, Journal: The development of cancers research based on mitochondrial heat shock protein 90. (Pubmed Central) - Dec 15, 2023
This review aims to provide a comprehensive overview of the present knowledge pertaining to mtHsp90, encompassing its structure and function. Moreover, our main emphasis is on the development of mtHsp90 inhibitors for various cancer therapies, to present a thorough overview of the recent pre-clinical and clinical advancements in this field.
- |||||||||| AZD8076 / AstraZeneca, Inovio, AZD5396 / Inovio, AstraZeneca
Enrollment open, Enrollment change, Trial completion date, Trial primary completion date: dMAbs for Prevention of COVID-19 (clinicaltrials.gov) - Sep 21, 2023
P1, N=39, Recruiting,
The properties of ALG-094103 will be further evaluated as a potential candidate for drug development. Active, not recruiting --> Recruiting | N=26 --> 39 | Trial completion date: Sep 2024 --> Sep 2025 | Trial primary completion date: Sep 2024 --> Sep 2025
- |||||||||| Covovax (NVX-CoV2373) / Novavax, Takeda, Serum Institute of India
Review, Journal: Vaccination is the most effective and best way to avoid the disease of COVID-19. (Pubmed Central) - Sep 3, 2023
Among the vaccines that stimulate the host's immune system with the help of DNA are: undergoing Phase 2/3 trials including INO-4800 (International Vaccine Institute; Inovio Pharmaceuticals), Symvivo, Canada-COVID19 (AnGes, Inc.); GX-19 (Genexine, Inc.). BNT162b2
- |||||||||| anti-PD-L1 therapy / The Wistar Institute
Journal, Checkpoint inhibition, PD(L)-1 Biomarker, IO biomarker: The African-centric P47S Variant of TP53 Confers Immune Dysregulation and Impaired Response to Immune Checkpoint Inhibition. (Pubmed Central) - Jul 17, 2023
Finally, we show that P47S mice demonstrate an incomplete response to anti-PD-L1 therapy...Findings presented here show that the P47S variant of TP53 influences the immune microenvironment, and the immune response to cancer. This is the first time that a naturally occurring genetic variant of TP53 has been shown to negatively impact the immune microenvironment and the response to immunotherapy.
- |||||||||| anti-PD-L1 therapy / The Wistar Institute, navitoclax (ABT 263) / AbbVie
Journal, PD(L)-1 Biomarker, IO biomarker: Patient-derived melanoma organoid models facilitate the assessment of immunotherapies. (Pubmed Central) - Jun 19, 2023
This is the first time that a naturally occurring genetic variant of TP53 has been shown to negatively impact the immune microenvironment and the response to immunotherapy. MPDOs may be used to test immune checkpoint inhibitors and cellular and targeted therapies.
- |||||||||| AZD8076 / AstraZeneca, Inovio, AZD5396 / Inovio, AstraZeneca
Enrollment closed, Trial completion date, Trial primary completion date: dMAbs for Prevention of COVID-19 (clinicaltrials.gov) - Apr 21, 2023
P1, N=26, Active, not recruiting,
MPDOs may be used to test immune checkpoint inhibitors and cellular and targeted therapies. Recruiting --> Active, not recruiting | Trial completion date: Nov 2023 --> Sep 2024 | Trial primary completion date: Nov 2023 --> Sep 2024
- |||||||||| anti-PD-L1 therapy / The Wistar Institute
Journal, PD(L)-1 Biomarker, IO biomarker: Targeting the mevalonate pathway suppresses ARID1A-inactivated cancers by promoting pyroptosis. (Pubmed Central) - Apr 12, 2023
In addition, simvastatin synergizes with anti-PD-L1 antibody in a genetic OCCC mouse model driven by conditional Arid1a inactivation and in a humanized immunocompetent ARID1A mutant patient-derived OCCC mouse model. Our data indicate that inhibition of the mevalonate pathway simultaneously suppresses tumor cell growth and boosts antitumor immunity by promoting pyroptosis, which synergizes with ICB in suppressing ARID1A-mutated cancers.
- |||||||||| Review, Journal: Nucleic acid-based vaccine platforms against the coronavirus disease 19 (COVID-19). (Pubmed Central) - Apr 4, 2023
Intracellular delivery of nucleic acid-based vaccines and their adverse events needs further research. Considering re-emergence of the COVID-19 variants of concern, vaccine reassessment and the development of polyvalent vaccines, or pan-coronavirus strategies, is essential for effective infection prevention.
- |||||||||| anti-PD-L1 therapy / The Wistar Institute
Preclinical, Journal, PD(L)-1 Biomarker, IO biomarker: Warming Menstruation and Analgesic Soup Inhibits PD-1/PD-L1 Pathway in Rats with Endometriosis. (Pubmed Central) - Mar 19, 2023
The protein and mRNA expression of PD-1 and PD-L1 in the eutopic and ectopic endothelium of the HW, MW and PC groups were lower than in the SG group (P <.05). High expression of PD-1 and PD-L1 occurs in endometriosis, and WMAS can inhibit the immune signalling pathway PD-1/PD-L1, which may be available to inhibit the development of endometriosis.
- |||||||||| anti-PD-L1 therapy / The Wistar Institute
Anti-Siglec 7 antibody displays potent anti-tumor immunity and demonstrates improved tumor control in combination with anti-PD1 in ovarian cancer (Section 31; Poster Board #12) - Mar 14, 2023 - Abstract #AACR2023AACR_6492;
Current immune checkpoint inhibitors (CPIs) have had modest impact for OC treatment; with anti PD-1/PD-L1 single therapies reported response rates of 4-15%...This is the first demonstration of the impact of Siglec 7 targeting mAb alone as well as in combination with anti-PD1 (NK and T cell CPIs) studied for targeting OC or any human tumor. These studies have important implications for tumor therapy and provide a novel non T cell CPI potential approach to augment current immune therapy strategies.
- |||||||||| gamitrinib / Fox Chase Cancer Center, The Wistar Institute
Synergistically suppressive effects by combination of glycolytic inhibitor with TRAP1-depletion in colorectal cancer (Section 10; Poster Board #6) - Mar 14, 2023 - Abstract #AACR2023AACR_2797;
To further elucidate the mechanistic role of TRAP1 in regulating tumor cell survival, we used gamitrinib-triphenylphosphonium (G-TPP) to inhibit TRAP1 signaling pathways in colon cancer...Taken together, depletion of TRAP1 induces mitochondrial dysfunction and modulates metabolic switch toward aerobic glycolysis in TRAP1-depleted colon cancer cells. Dual inhibition of TRAP1 and glycolytic signaling may increase therapeutic efficiency through induction of excessive ROS production in colon cancer.
- |||||||||| anti-PD-L1 therapy / The Wistar Institute
Journal, PD(L)-1 Biomarker, IO biomarker: High PD-L2 Predicts Early Recurrence of ER-Positive Breast Cancer. (Pubmed Central) - Jan 19, 2023
Up to one third of treatment-naive ER+ breast tumors expressed high PD-L2 levels, which independently predicted poor clinical outcome, with evidence of further elevated risk of progression in patients who received adjuvant chemotherapy. Collectively, these data warrant studies to gain a deeper understanding of PD-L2 in the progression of ER+ breast cancer and may provide rationale for immune checkpoint blockade for this patient group.
- |||||||||| anti-PD-L1 therapy / The Wistar Institute
Journal: Targeting the secreted RGDKGE collagen fragment reduces PD‑L1 by a proteasome‑dependent mechanism and inhibits tumor growth. (Pubmed Central) - Jan 13, 2023
Selectively targeting this collagen fragment, reduced nuclear YAP levels, and enhanced PKA and proteasome activity, while also exhibiting significant antitumor activity in vivo. The present findings not only provided new mechanistic insight into a previously unknown autocrine‑like signaling pathway that may provide tumor cells with the ability to regulate PD‑L1, but our findings may also help in the development of more effective strategies to control pro‑tumorigenic β3‑integrin signaling without disrupting its tumor suppressive functions in other cellular compartments.
- |||||||||| INO-4800 / Inovio, The Wistar Institute, INO-9112 / Inovio
Enrollment change, Trial withdrawal, Combination therapy: Safety, Tolerability and Immunogenicity of INO-4800 for COVID19 in Healthy Volunteers (clinicaltrials.gov) - Nov 17, 2022
P1, N=0, Withdrawn,
The present findings not only provided new mechanistic insight into a previously unknown autocrine‑like signaling pathway that may provide tumor cells with the ability to regulate PD‑L1, but our findings may also help in the development of more effective strategies to control pro‑tumorigenic β3‑integrin signaling without disrupting its tumor suppressive functions in other cellular compartments. N=160 --> 0 | Not yet recruiting --> Withdrawn
- |||||||||| gamitrinib / Fox Chase Cancer Center, The Wistar Institute
Journal, PARP Biomarker: Metabolic targeting of NRF2 potentiates the efficacy of the TRAP1 inhibitor G-TPP through reduction of ROS detoxification in colorectal cancer. (Pubmed Central) - Oct 18, 2022
To further elucidate the mechanistic role of TRAP1 in regulating tumor cell survival, we used gamitrinib-triphenylphosphonium (G-TPP) to inhibit TRAP1 signaling pathways in colon cancer...Furthermore, treatment with both a NRF2 inhibitor and a TRAP1 inhibitor led to excessive ROS production and exacerbated G-TPP-induced cell death in G-TPP-resistant cells. Taken together, dual targeting of TRAP1 and NRF2 may potentially overcome colon cancer resistance by raising cellular ROS levels above the cytotoxic threshold.
- |||||||||| INO-4800 / Inovio, The Wistar Institute
Enrollment change, Trial completion date, Trial termination, Trial primary completion date: INNOVATE: Safety, Immunogenicity, and Efficacy of INO-4800 for COVID-19 in Adults at High Risk of SARS-CoV-2 Exposure (clinicaltrials.gov) - Oct 13, 2022
P2/3, N=1308, Terminated,
Taken together, dual targeting of TRAP1 and NRF2 may potentially overcome colon cancer resistance by raising cellular ROS levels above the cytotoxic threshold. N=7517 --> 1308 | Trial completion date: Feb 2023 --> Sep 2022 | Active, not recruiting --> Terminated | Trial primary completion date: Feb 2023 --> Sep 2022; The study was terminated to prioritize Inovio's COVID-19 efforts to advance a heterologous booster strategy and optimize potential impact on global public health.
- |||||||||| gamitrinib / Fox Chase Cancer Center, The Wistar Institute
Review, Journal: Targeting HSP90 as a Novel Therapy for Cancer: Mechanistic Insights and Translational Relevance. (Pubmed Central) - Oct 1, 2022
Here, we review the subcellular localization of HSP90, its corresponding mechanism of action in the malignant phenotypes, and the recent progress on the development of HSP90 inhibitors. Hopefully, this comprehensive review will shed light on the translational potential of HSP90 inhibitors as novel cancer therapeutics.
- |||||||||| gamitrinib / Fox Chase Cancer Center, The Wistar Institute, etomoxir (MIQ-001) - Meta / IQ
Loss of function of CDK7 is synthetically lethal with fatty acid oxidation inhibition in glioblastoma (West/Central Hall) - Sep 28, 2022 - Abstract #SNO2022SNO_1167;
Finally, the combined administration of YKL-5-124 and etomoxir extended overall in an orthotopic patient-derived xenograft model of GBM. In summary, these data support that simultaneous targeting of CDK7 and FAO might be a potential novel therapy against GBM.
- |||||||||| INO-4800 / Inovio, The Wistar Institute, INO-9112 / Inovio
Trial completion date, Trial primary completion date, Combination therapy: Safety, Tolerability and Immunogenicity of INO-4800 for COVID19 in Healthy Volunteers (clinicaltrials.gov) - Aug 22, 2022
P1, N=160, Not yet recruiting,
In summary, these data support that simultaneous targeting of CDK7 and FAO might be a potential novel therapy against GBM. Trial completion date: Aug 2023 --> Mar 2024 | Trial primary completion date: Aug 2023 --> Mar 2024
- |||||||||| INO-4800 / Inovio, The Wistar Institute
INO-4800 ? (Twitter) - Aug 20, 2022
- |||||||||| anti-PD-L1 therapy / The Wistar Institute
Journal, PD(L)-1 Biomarker, IO biomarker: HRS phosphorylation drives immunosuppressive exosome secretion and restricts CD8 T-cell infiltration into tumors. (Pubmed Central) - Jul 23, 2022
In murine tumor models, overexpression of phosphorylated HRS increases resistance to anti-PD-1 treatment, whereas inhibition of HRS phosphorylation enhances treatment efficacy. Our study reveals a mechanism by which phosphorylation of HRS in tumor cells regulates anti-tumor immunity by inducing PD-L1 immunosuppressive exosomes, and suggests HRS phosphorylation blockade as a potential strategy to improve the efficacy of cancer immunotherapy.
- |||||||||| INO-4800 / Inovio, The Wistar Institute
Trial completion, Enrollment change, Trial completion date: Safety, Tolerability and Immunogenicity of INO-4800 Followed by Electroporation in Healthy Volunteers for COVID19 (clinicaltrials.gov) - Jul 18, 2022
P1/2, N=79, Completed,
Our study reveals a mechanism by which phosphorylation of HRS in tumor cells regulates anti-tumor immunity by inducing PD-L1 immunosuppressive exosomes, and suggests HRS phosphorylation blockade as a potential strategy to improve the efficacy of cancer immunotherapy. Recruiting --> Completed | N=160 --> 79 | Trial completion date: Feb 2022 --> May 2022
- |||||||||| anti-PD-L1 therapy / The Wistar Institute
Preclinical, Journal, PD(L)-1 Biomarker, IO biomarker: Preclinical platforms to study therapeutic efficacy of human γδ T cells. (Pubmed Central) - Jun 29, 2022
Checkpoint inhibitors and epigenetic modifiers enhance anti-tumour functions of γδ T cells. These four 3D models provided valuable preclinical platforms to test γδ T cell functions for immunotherapy.
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