Anti-ErbB2 immunotherapeutics: struggling to make better antibodies for cancer therapy

Santis, Rita De

doi:10.1080/19420862.2020.1725346

Cited by 23 publications

(12 citation statements)

References 70 publications

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“…Thus, the tolerability, safety, pharmacodynamics, pharmacokinetics, and preliminary activity profile of RO7119929 administered as standalone therapeutic intervention are being evaluated in patients with unresectable advanced or metastatic hepatocellular carcinoma (HCC), biliary tract cancer, or other solid tumors with predominant liver involvement and metastases (NCT04338685). Similarly, the erb-b2 receptor tyrosine kinase 2 (ERBB2, best known as HER2)-targeted TLR7 agonistic ISAC NJH395 115,116 is being tested as monotherapy in patients with nonbreast HER2 + advanced solid neoplasms (NCT03696771). Along similar lines, the HER2-targeted TLR7/TLR8 mixed agonist ISAC BDC-1001 is being evaluated in a first-in-human trials enrolling individuals with HER2 + breast and gastric carcinoma (NCT04278144).…”

Section: Ongoing Clinical Trialsmentioning

confidence: 99%

Trial Watch: experimental TLR7/TLR8 agonists for oncological indications

Frega

Naour

et al. 2020

OncoImmunology

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Resiquimod (R848) and motolimod (VTX-2337) are second-generation experimental derivatives of imiquimod, an imidazoquinoline with immunostimulatory properties originally approved by the US Food and Drug Administration for the topical treatment of actinic keratosis and genital warts more than 20 years ago. Both resiquimod and motolimod operate as agonists of Toll-like receptor 7 (TLR7) and/or TLR8, in thus far delivering adjuvant-like signals to antigen-presenting cells (APCs). In line with such an activity, these compounds are currently investigated as immunostimulatory agents for the treatment of various malignancies, especially in combination with peptide-based, dendritic cell-based, cancer cell lysate-based, or DNA-based vaccines. Here, we summarize preclinical and clinical evidence recently collected to support the development of resiquimod and motolimod and other TLR7/TLR8 agonists as anticancer agents.

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Section: Ongoing Clinical Trialsmentioning

confidence: 99%

Trial Watch: experimental TLR7/TLR8 agonists for oncological indications

Frega

Naour

et al. 2020

OncoImmunology

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“…Among the number of HER2 -directed agents, there is a growing attention towards MT-5111, an immunotoxin whose action is based on the use of a Shiga-like toxin to enter into HER2 -positive cells [ 47 ]; notably enough, preclinical reports have suggested that MT-5111 could be combined safely with trastuzumab, and MT-5111 is being investigated in breast cancer and GC patients [ 48 ].…”

Section: Zw25 Tucatinib and Other Her2-targeted Agentsmentioning

confidence: 99%

Novel HER2-Directed Treatments in Advanced Gastric Carcinoma: AnotHER Paradigm Shift?

Ricci

Rizzo

Llimpe

et al. 2021

Cancers

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Human epidermal growth factor receptor 2 (HER2) is overexpressed and/or amplified in approximately 15–20% of gastric adenocarcinoma (GC) patients. In 2010, the landmark ToGA trial established the combination of trastuzumab plus chemotherapy as the first-line standard of care for HER2-positive GC patients with advanced disease. However, subsequent studies on HER2 targeted therapies in this setting failed to meet their primary endpoints, and not all HER2-positive GC patients benefit from targeted approaches. More recently, novel HER2-directed treatments have been investigated, including trastuzumab deruxtecan (T-Dxd); following the results of the DESTINY-Gastric01 study, T-Dxd received its first U.S. Food and Drug Administration (FDA) approval on 15 January 2021 for the treatment of adults with unresectable, locally advanced, or metastatic GC who have received a prior trastuzumab-based regimen. In this review, we discuss the current HER2-targeted treatments for GC in the advanced disease setting, mainly focusing on emerging new treatments and future research directions.

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“…Although these drug combinations showed no clinical benefit in the Mypathway trial with HER2 amplification in endometrial cancer[ 25 ], further investigation is warranted. Several HER2 bispecific antibodies have been developed that simultaneously bind to two distinct HER2 epitopes, the same domain as trastuzumab and pertuzumab[ 73 ]. Researchers demonstrated a phase 1 basket trial to evaluate ZW25, one of HER2 bispecific antibodies, in HER2 positive solid tumors, including endometrial cancer.…”

Section: Current Therapies and Future Directions For Her2 Targeted Therapies For Uterine Serous Carcinoma And Uterine Carcinosarcomamentioning

confidence: 99%

“…PRS-343 increases tumor lymphocyte invasion via targeting HER2 and CD137 (4-1BB). CD137 is known as a co-stimulating factor of T cell activation[ 73 ]. We expect a further investigation of these drugs in patients with endometrial cancer.…”

Section: Current Therapies and Future Directions For Her2 Targeted Therapies For Uterine Serous Carcinoma And Uterine Carcinosarcomamentioning

confidence: 99%

Human epidermal growth factor receptor 2 targeted therapy in endometrial cancer: Clinical and pathological perspectives

Saito¹,

Yoshida²,

Nishikawa³

et al. 2021

WJCO

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Endometrial cancer is the most common gynecological cancer in developed countries, and its incidence has increased. The majority of patients with endometrial cancer have an early disease and favorable prognosis; however, a significant proportion of endometrial cancer, which mainly comprises high-grade or type II endometrial cancer such as serous, clear cell, and carcinosarcoma, shows advanced/recurrent disease and dismal prognosis. Novel therapeutic development is required for patients with aggressive endometrial cancers. Recent genomic and immunohistochemical analyses revealed human epidermal growth factor receptor 2 (HER2) overexpression/gene amplification in 20%-40% of patients with type II endometrial cancer. Historically, HER2 targeted therapy has been developed for various major cancers, including breast and gastric cancer. Notably, recent advances in HER2 targeted therapy for patients with type II endometrial cancer are also expected to change. Simultaneously, an optimized HER2 test for endometrial cancer as companion diagnostics should be established. In this review, we summarize the recent findings on endometrial cancer, current treatment, optimized HER2 testing, key clinical trials on HER2 targeted therapy, and future directions in aggressive endometrial cancer, including serous carcinoma and carcinosarcoma.

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Anti-ErbB2 immunotherapeutics: struggling to make better antibodies for cancer therapy

Cited by 23 publications

References 70 publications

Trial Watch: experimental TLR7/TLR8 agonists for oncological indications

Trial Watch: experimental TLR7/TLR8 agonists for oncological indications

Novel HER2-Directed Treatments in Advanced Gastric Carcinoma: AnotHER Paradigm Shift?

Human epidermal growth factor receptor 2 targeted therapy in endometrial cancer: Clinical and pathological perspectives

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