LY3022855, an anti–colony stimulating factor-1 receptor (CSF-1R) monoclonal antibody, in patients with advanced solid tumors refractory to standard therapy: phase 1 dose-escalation trial

Dowlati, Afshin; Harvey, R. Donald; Carvajal, Richard D.; Hamid, Omid; Klempner, Samuel J.; Kauh, John S.; Peterson, Daniel A.; Yu, Danni; Chapman, Sonya C.; Szpurka, Anna M.; Carlsen, Michelle; Quinlan, Tonya; Wesolowski, Robert

doi:10.1007/s10637-021-01084-8

Cited by 31 publications

(12 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Studies have found that certain drugs such as emactuzumab and IMC-CS4 can inhibit tumor development by reducing the number of macrophages ( 8 , 9 ). In addition, primary tumors express CCL2 and CCR2, recruiting TAM.…”

Section: Macrophagesmentioning

confidence: 99%

The role of innate immune cells in the tumor microenvironment and research progress in anti-tumor therapy

Liu

Ali

et al. 2023

Front. Immunol.

View full text Add to dashboard Cite

Innate immune cells in the tumor microenvironment (TME) mainly include macrophages, neutrophils, natural killer cells, dendritic cells and bone marrow derived suppressor cells. They play an anti-tumor or pro-tumor role by secreting various cytokines, chemokines and other factors, and determine the occurrence and development of tumors. Comprehending the role of innate immune cells in tumorigenesis and progression can help improve therapeutic approaches targeting innate immune cells in the TME, increasing the likelihood of favorable prognosis. In this review, we discussed the cell biology of innate immune cells, their role in tumorigenesis and development, and the current status of innate immune cell-based immunotherapy, in order to provide an overview for future research lines and clinical trials.

show abstract

Section: Macrophagesmentioning

confidence: 99%

The role of innate immune cells in the tumor microenvironment and research progress in anti-tumor therapy

Liu

Ali

et al. 2023

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…However, few have been able to demonstrate meaningful clinical activity. Two phase I trials involving LY3022855 monotherapy (NCT02265536, NCT01346358) and one phase I trial involving AMG 820 (NCT01444404) in the management of advanced solid tumors reported zero objective responses (0/86 and 0/25, respectively), though decreases in TAMs were noted in addition to elevations in circulation CSF-1 levels, indicating that proper target engagement occurred [179][180][181]. When LY302285 is used in combination with ICIs including tremelimumab (anti-CTLA-4) or durvalumab (anti-PD-L1), ORR approaches 4.2% (3/72) [182].…”

Section: Csf-1rmentioning

confidence: 99%

Emerging strategies in targeting tumor-resident myeloid cells for cancer immunotherapy

Wang

Johnson²,

Gatti‐Mays

et al. 2022

J Hematol Oncol

View full text Add to dashboard Cite

Immune checkpoint inhibitors targeting programmed cell death protein 1, programmed death-ligand 1, and cytotoxic T-lymphocyte-associated protein 4 provide deep and durable treatment responses which have revolutionized oncology. However, despite over 40% of cancer patients being eligible to receive immunotherapy, only 12% of patients gain benefit. A key to understanding what differentiates treatment response from non-response is better defining the role of the innate immune system in anti-tumor immunity and immune tolerance. Teleologically, myeloid cells, including macrophages, dendritic cells, monocytes, and neutrophils, initiate a response to invading pathogens and tissue repair after pathogen clearance is successfully accomplished. However, in the tumor microenvironment (TME), these innate cells are hijacked by the tumor cells and are imprinted to furthering tumor propagation and dissemination. Major advancements have been made in the field, especially related to the heterogeneity of myeloid cells and their function in the TME at the single cell level, a topic that has been highlighted by several recent international meetings including the 2021 China Cancer Immunotherapy workshop in Beijing. Here, we provide an up-to-date summary of the mechanisms by which major myeloid cells in the TME facilitate immunosuppression, enable tumor growth, foster tumor plasticity, and confer therapeutic resistance. We discuss ongoing strategies targeting the myeloid compartment in the preclinical and clinical settings which include: (1) altering myeloid cell composition within the TME; (2) functional blockade of immune-suppressive myeloid cells; (3) reprogramming myeloid cells to acquire pro-inflammatory properties; (4) modulating myeloid cells via cytokines; (5) myeloid cell therapies; and (6) emerging targets such as Siglec-15, TREM2, MARCO, LILRB2, and CLEVER-1. There is a significant promise that myeloid cell-based immunotherapy will help advance immuno-oncology in years to come.

show abstract

“…Among patients with diffuse type TGCT, instead, emactuzumab therapy resulted in improved and durable clinical responses, as well as in quality-of-life assessment [ 38 ]. LY3022855, a human immunoglobulin G subclass 1 (IgG1) anti-CSF1R mAb, has been tested alone (NCT01346358) or in combination with tremelimumab (NCT02718911) in patients with advanced solid tumors, demonstrating limited clinical activity despite a good safety profile [ 39 , 40 ].…”

Section: Targeting Immune System In Cancermentioning

confidence: 99%

Targeting Cellular Components of the Tumor Microenvironment in Solid Malignancies

Belli

Antonarelli

Repetto

et al. 2022

Cancers

View full text Add to dashboard Cite

Cancers are composed of transformed cells, characterized by aberrant growth and invasiveness, in close relationship with non-transformed healthy cells and stromal tissue. The latter two comprise the so-called tumor microenvironment (TME), which plays a key role in tumorigenesis, cancer progression, metastatic seeding, and therapy resistance. In these regards, cancer-TME interactions are complex and dynamic, with malignant cells actively imposing an immune-suppressive and tumor-promoting state on surrounding, non-transformed, cells. Immune cells (both lymphoid and myeloid) can be recruited from the circulation and/or bone marrow by means of chemotactic signals, and their functionality is hijacked upon arrival at tumor sites. Molecular characterization of tumor-TME interactions led to the introduction of novel anti-cancer therapies targeting specific components of the TME, such as immune checkpoint blockers (ICB) (i.e., anti-programmed death 1, anti-PD1; anti-Cytotoxic T-Lymphocyte Antigen 4, anti-CTLA4). However, ICB resistance often develops and, despite the introduction of newer technologies able to study the TME at the single-cell level, a detailed understanding of all tumor-TME connections is still largely lacking. In this work, we highlight the main cellular and extracellular components of the TME, discuss their dynamics and functionality, and provide an outlook on the most relevant clinical data obtained with novel TME-targeting agents, with a focus on T lymphocytes, macrophages, and cancer-associated fibroblasts.

show abstract

LY3022855, an anti–colony stimulating factor-1 receptor (CSF-1R) monoclonal antibody, in patients with advanced solid tumors refractory to standard therapy: phase 1 dose-escalation trial

Cited by 31 publications

References 28 publications

The role of innate immune cells in the tumor microenvironment and research progress in anti-tumor therapy

The role of innate immune cells in the tumor microenvironment and research progress in anti-tumor therapy

Emerging strategies in targeting tumor-resident myeloid cells for cancer immunotherapy

Targeting Cellular Components of the Tumor Microenvironment in Solid Malignancies

Contact Info

Product

Resources

About