The Role of Bispecific Antibodies in Non-Hodgkin’s Lymphoma: From Structure to Prospective Clinical Use

Tavarozzi, Rita; Manzato, Enrica

doi:10.3390/antib11010016

Cited by 7 publications

(5 citation statements)

References 60 publications

(117 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The definition of the starting dose of 50 µg for CC-3 was based on preclinical data derived from CC-3 dose titrations of in vitro T-cell activation and cytokine release, in comparison with pharmacokinetic (PK) data from a clinical study with CC-1 (a bsAb with PSMAxCD3 specificity of otherwise identical format), as well as on clinical experience and clinical studies with MGD009 [a bsAb with CD276xCD3 specificity in a different format ( 34 )] and CD20xCD3 bsAb ( 35 ). The maximum dose of 4,000 µg of CC-3 was derived from an in vivo model with humanized NOD scid gamma (NSG) mice, in which repetitive dosing with 1.4 µg of CC-3 achieved an eradication of established flank tumors.…”

Section: Methods and Analysismentioning

confidence: 99%

Protocol of a first-in-human clinical trial to evaluate the safety, tolerability, and preliminary efficacy of the bispecific CD276xCD3 antibody CC-3 in patients with colorectal cancer (CoRe_CC-3)

Jung,

Schlenk,

Hackenbruch

et al. 2024

Front. Oncol.

View full text Add to dashboard Cite

IntroductionColorectal cancer (CRC) is the third most common cancer worldwide in men and women. In the metastasized stage, treatment options and prognosis are limited. To address the high medical need of this patient population, we generated a CD276xCD3 bispecific antibody termed CC-3. CD276 is expressed on CRC cells and on tumor vessels, thereby allowing for a “dual” anticancer effect.Methods and analysisThis first-in-human clinical study is planned as a prospective multicenter trial, enrolling patients with metastatic CRC after three lines of therapy. During the dose-escalation part, initially, an accelerated titration design with single-patient cohorts is employed. Here, each patient will receive a fixed dose level (starting with 50 µg for the first patient); however, between patients, dose level may be increased by up to 100%, depending on the decision of a safety review committee. Upon occurrence of any adverse events (AEs) grade ≥2, dose-limiting toxicity (DLT), or reaching a dose level of ≥800 µg, the escalation will switch to a standard 3 + 3 dose design. After maximum tolerated dose (MTD) has been determined, defined as no more than one of the six patients experiencing DLT, an additional 14 patients receive CC-3 at the MTD level in the dose-expansion phase. Primary endpoints are incidence and severity of AEs, as well as the best objective response to the treatment according to response evaluation criteria in solid tumors (RECIST) 1.1. Secondary endpoints include overall safety, efficacy, survival, quality of life, and pharmacokinetic investigations.Ethics and disseminationThe CD276xCD3 study was approved by the Ethics Committee of the Medical Faculty of the Heinrich Heine University Düsseldorf and the Paul-Ehrlich-Institut (P00702). Clinical trial results will be published in peer-reviewed journals. Trial registration numbers: ClinicalTrials.cov Registry (NCT05999396) and EU ClinicalTrials Registry (EU trial number 2022-503084-15-00).

show abstract

Section: Methods and Analysismentioning

confidence: 99%

Protocol of a first-in-human clinical trial to evaluate the safety, tolerability, and preliminary efficacy of the bispecific CD276xCD3 antibody CC-3 in patients with colorectal cancer (CoRe_CC-3)

Jung,

Schlenk,

Hackenbruch

et al. 2024

Front. Oncol.

View full text Add to dashboard Cite

show abstract

“…This subclass includes bispecific T-cell engagers, dual-affinity re-targeting antibodies (DARTs), and tetravalent tandem diabodies (TandAb) [17].…”

Section: Non-igg-like Bsabsmentioning

confidence: 99%

“…However, they have better tumour penetration secondary to their small size and are easier to manufacture when compared to IgG-like antibodies [20]. Additionally, they do not exhibit antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), or complement fixation due to absence of the Fc-portion [17].…”

Section: Non-igg-like Bsabsmentioning

confidence: 99%

T-Cell Engaging Antibodies in Diffuse Large B Cell Lymphoma—An Update

Balendran,

Tam,

2023

JCM

View full text Add to dashboard Cite

Novel cellular immunotherapies such as T-cell engaging antibodies (TCEAbs) are changing the landscape of treatment for diffuse large B cell lymphoma (DLBCL), especially in the relapsed/refractory (R/R) setting. TCEAbs harness the power of the host immune system to induce killing of tumor cells by binding to both the tumor antigen and the T-cell receptor. Since the approval of blinatumomab for R/R acute lymphoblastic leukemia, there has been significant development in novel TCEAbs. Many of these novel TCEAbs have shown promising effectiveness in R/R DLBCL, with favorable response rates including complete remissions, even in heavily pretreated patients. There are unique therapy-related toxicities with TCEAbs, namely cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity (ICANS), and it is important to both recognize and manage these side effects appropriately. This review examines the development and mechanism of action of these TCEAbs, and the available published data from clinical trials. Their role in the treatment of DLBCL, the management of therapy-related adverse events, and the mechanisms of resistance will also be discussed.

show abstract

“…Several non-IgG-like bsAbs are being tested in human trials with different formats, such as bispecific T-or killer-cell engagers (BiTEs or BiKEs), dual-affinity re-targeting antibodies (DARTs), and tandem diabodies (TandAbs). In contrast, most IgG-like bsAbs are in use or about to be utilized for the treatment of B-NHL (e.g., mosunetuzumab, odronextamab, and epcoritamab) [19].…”

Section: The Phylogenic Tree: From Murine Models To Novel Immunothera...mentioning

confidence: 99%

Changing Trends in B-Cell Non-Hodgkin Lymphoma Treatment: The Role of Novel Monoclonal Antibodies in Clinical Practice

Tavarozzi,

Zacchi,

Pietrasanta

et al. 2023

Cancers

Self Cite

View full text Add to dashboard Cite

We are currently witnessing a dramatic shift in our approach to the treatment of B-cell non-Hodgkin lymphoma (B-NHL). In the evolving clinical landscape, novel treatments for this clinically heterogeneous disease span a wide range of interventions, encompassing targeted agents, cell therapy approaches, and novel monoclonal antibodies (NMABs). Among these, the latter are likely to exert the most profound impact due to their distinctive high efficacy and versatile applicability. NMABs represent a heterogeneous group of agents, including naked antibodies, immunotoxins, and T-cell-engaging molecules. In recent times, several NMABs have either gained regulatory approval or are on the verge of introduction into clinical practice, addressing multiple therapeutic indications and treatment regimens. Their anticipated impact is expected to be broad, initially in the context of relapsed/refractory (R/R) disease and subsequently extending to early treatment lines. The scope of this review is to provide a comprehensive overview of the biological characteristics, clinical properties, efficacy, and toxicity profiles of NMABs that have recently been introduced or are nearing integration into clinical practice.

show abstract

The Role of Bispecific Antibodies in Non-Hodgkin’s Lymphoma: From Structure to Prospective Clinical Use

Cited by 7 publications

References 60 publications

Protocol of a first-in-human clinical trial to evaluate the safety, tolerability, and preliminary efficacy of the bispecific CD276xCD3 antibody CC-3 in patients with colorectal cancer (CoRe_CC-3)

Protocol of a first-in-human clinical trial to evaluate the safety, tolerability, and preliminary efficacy of the bispecific CD276xCD3 antibody CC-3 in patients with colorectal cancer (CoRe_CC-3)

T-Cell Engaging Antibodies in Diffuse Large B Cell Lymphoma—An Update

Changing Trends in B-Cell Non-Hodgkin Lymphoma Treatment: The Role of Novel Monoclonal Antibodies in Clinical Practice

Contact Info

Product

Resources

About