Development of Lu‐177‐trastuzumab for radioimmunotherapy of HER2 expressing breast cancer and its feasibility assessment in breast cancer patients

Bhusari, Priya; Vatsa, Rakhee; Singh, Gurpreet; Parmar, Madan; Bal, Amanjit; Dhawan, D. K.; Mittal, Bhagwant Rai; Shukla, Jaya

doi:10.1002/ijc.30500

Cited by 61 publications

(81 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A pilot study evaluated the feasibility of treating HER2+ mBC patients refractory to previous therapies with radioimmunotherapy developed by attaching the radioactive lutetium-177 (Lu-177) to trastuzumab. This study showed that the treatment was feasible and safe and could be considered for palliative treatment of HER2+ mBC in combination with standard agents [132].…”

Section: Enhancing the Her2-block Immune-mediated Mechanismmentioning

confidence: 99%

Immunotherapy in HER2-positive breast cancer: state of the art and future perspectives

et al. 2019

View full text Add to dashboard Cite

Breast cancer (BC) is a complex disease with primary or acquired incurability characteristics in a significant part of patients. Immunotherapeutical agents represent an emerging option for breast cancer treatment, including the human epidermal growth factor 2 positive (HER2+) subtype. The immune system holds the ability to spontaneously implement a defensive response against HER2+ BC cells through complex mechanisms which can be exploited to modulate this response for obtaining a clinical benefit. Initial immune system modulating strategies consisted mostly in vaccine therapies, which are still being investigated and improved. However, the entrance of trastuzumab into the scenery of HER2+ BC treatment was the real game changing event, which embodied a dominant immune-mediated mechanism. More recently, the advent of the immune checkpoint inhibitors has caused a new paradigm shift for immuno-oncology, with promising initial results also for HER2+ BC. Breast cancer has been traditionally considered poorly immunogenic, being characterized by relatively low tumor mutation burden (TMB). Nevertheless, recent evidence has revealed high tumor infiltrating lymphocytes (TILs) and programmed cell death-ligand 1 (PD-L1) expression in a considerable proportion of HER2+ BC patients. This may translate into a higher potential to elicit anti-cancer response and, therefore, wider possibilities for the use and implementation of immunotherapy in this subset of BC patients. We are herein presenting and critically discussing the most representative evidence concerning immunotherapy in HER2+ BC cancer, both singularly and in combination with therapeutic agents acting throughout HER2-block, immune checkpoint inhibition and anti-cancer vaccines. The reader will be also provided with hints concerning potential future projection of the most promising immutherapeutic agents and approaches for the disease of interest.

show abstract

Section: Enhancing the Her2-block Immune-mediated Mechanismmentioning

confidence: 99%

Immunotherapy in HER2-positive breast cancer: state of the art and future perspectives

et al. 2019

View full text Add to dashboard Cite

show abstract

“…This antibody has been labeled with 177 Lu, 64 Cu, 111 In,Thorium-227 ( 227 Th), Rhenium-188 ( 188 Re), Yttrium-90 ( 90 Y), and Iodine-131 ( 131 I). 34 –37,45,63 –66…”

Section: Targeting Of Her2 For Radionuclide Therapymentioning

confidence: 99%

Targeting HER2 in Nuclear Medicine for Imaging and Therapy

2018

View full text Add to dashboard Cite

Since its discovery, the human epidermal growth factor 2 (HER2) has been extensively studied. Presently, there are 2 standard diagnostic techniques to assess HER2 status in biopsies: immunohistochemistry and fluorescence in situ hybridization. While these techniques have played an important role in the treatment of patients with HER2-positive cancer, they both require invasive biopsies for analysis. Moreover, the expression of HER2 is heterogeneous in breast cancer and can change over the course of the disease. Thus, the degree of HER2 expression in the small sample size of biopsied tumors at the time of analysis may not represent the overall status of HER2 expression in the whole tumor and in between tumor foci in the metastatic setting as the disease progresses. Unlike biopsy, molecular imaging using probes against HER2 allows for a noninvasive, whole-body assessment of HER2 status in real time. This technique could potentially select patients who may benefit from HER2-directed therapy and offer alternative treatments to those who may not benefit. Several antibodies and small molecules against HER2 have been labeled with different radioisotopes for nuclear imaging and/or therapy. This review presents the most recent advances in HER2 targeting in nuclear medicine focusing on preclinical and clinical studies.

show abstract

“…Bhusari and coworkers developed a 177 Lu-trastuzumab tracer for radioimmunotherapy of HER2 expressing breast cancer and also explored its potential as an imaging agent. 53 This study demonstrated that the development, characterization and radiolabeling of 177 Lu-trastuzumab can be efficiently achieved in-house and that this radiotracer is safe to be administered to the patients. The HER2 positive primary and metastatic breast lesions specifically take up 177 Lu-trastuzumab, with two patient examples shown in Figures 7 (Day 1 and Day 7 time points) and Figure 8 (Day 5).…”

Section: Pet and Spect Imaging With Monoclonal Antibodies In Her2-posmentioning

confidence: 80%

Clinical Potential of Human Epidermal Growth Factor Receptor 2 and Human Epidermal Growth Factor Receptor 3 Imaging in Breast Cancer

2018

View full text Add to dashboard Cite

Increased expression of the human epidermal growth factor receptor (HER) protein family are targets in breast cancer for imaging and therapy. Imaging modalities targeting HER2 and HER3 can diagnose breast cancer with a specific, biologically relevant target. Repeat biopsies do not address heterogeneity intratumorally or between primary disease and metastasis. HER2- and HER3-targeted PET is an important tool to diagnose disease in breast cancer and evaluate response to targeted therapies. PET and single photon emission computed tomography with radiolabeled biomolecules can be used to detect and quantify specific targets, conferring a better understanding of the behavior and effectiveness of treatments.

show abstract

Development of Lu‐177‐trastuzumab for radioimmunotherapy of HER2 expressing breast cancer and its feasibility assessment in breast cancer patients

Cited by 61 publications

References 25 publications

Immunotherapy in HER2-positive breast cancer: state of the art and future perspectives

Immunotherapy in HER2-positive breast cancer: state of the art and future perspectives

Targeting HER2 in Nuclear Medicine for Imaging and Therapy

Clinical Potential of Human Epidermal Growth Factor Receptor 2 and Human Epidermal Growth Factor Receptor 3 Imaging in Breast Cancer

Contact Info

Product

Resources

About