Modeling human acute lymphoblastic leukemia (ALL) – using the NALM6-Luc-mCh-Puro model for the development of CAR T cell therapies

Acute lymphoblastic leukemia (ALL) is a cancer of the lymphoid lineage characterized by the development of increased numbers of immature lymphocytes. ALL is a relatively rare cancer, representing less than 0.5% of all cancers in the United States, with the American Cancer Society estimating approximately 5,930 new cases and 1,500 deaths from ALL in the United States for 2019. However, the fact that ALL is the most common childhood cancer makes it of interest to researchers. The risk for developing ALL is highest in children younger than 5 years of age. This risk then declines slowly until the mid-20s before it begins to rise again after age 50. While most cases of ALL occur in children, most deaths from ALL occur in adults. Standard therapies for ALL include the use of aggressive or long-term chemotherapy. These treatment regimens result in 90% of children surviving after five years. However, this drops to around 40% of adult patients remaining disease free. Due to this relapse rate in ALL, other treatment options have been sought.

C1498: A murine model for acute myelogenous leukemia (AML)

Acute myelogenous leukemia (AML) is a rapidly progressing malignancy of myeloid white blood cells.  An estimated 21,380 new cases of AML and 10,590 deaths will occur in the United States in 2017. AML results from excessive proliferation of dedifferentiated or undifferentiated myeloid leukocytes initially in the bone marrow. As disease progresses, AML blast cells will be found in the blood and other secondary lymphoid organs. Symptoms including anemia and leukopenia result from proliferating AML cells suppressing normal hematopoiesis in the bone marrow. AML is characterized by a complex number of subtypes that are defined by genomic alterations and gene expression profiling. Treatment typically starts with intensive chemotherapy followed by allogeneic bone marrow transplantation (BMT) in patients that can tolerate these therapies. Less debilitating treatment options, including immunotherapy, are needed for older AML patients who frequently cannot tolerate intensive chemotherapy or BMT.

A New Labcorp Offering: Predictive Oncology® Reconstructed Bone (r-Bone), plate-based, 3-dimensional (3D) culture assay that mimics the tumor microenvironment found in myeloma, acute myelogenous leukemia and solid tumor metastasis.

In order to provide a more reflective model of how tumor cells would respond to test agents in vivo, the tissue physiology where the tumor grows and proliferates needs to be recapitulated in vitro. This process has been accomplished using Predictive Oncology® organ-specific three-dimensional (3D) matrices that support long-term culture of carcinoma cells. Labcorp and Predictive Oncology® have worked together to develop tumor-specific 3D models, based on Predictive Oncology® proprietary 3D cell culture platform for preclinical testing and research studies in the biopharmaceutical industry. This tech spotlight highlights the characteristics of the Reconstructed Bone (r-Bone) model.

B16-F10: a murine melanoma model

Skin cancers include carcinomas of all layers of the skin with the most common being basal cell (BCC) and squamous cell carcinomas (SCC). Melanoma and non-melanoma skin cancers (Merkel cell carcinoma, Kaposi sarcoma, cutaneous lymphoma and other sarcomas) are much less common.  Of all the skin cancer types, melanoma is a serious form of skin cancer that begins in melanocytes, the melanin-producing neural crest-derived cells located in the bottom layer (the stratum basale) of the skin’s epidermis. While malignant BCC and SCC are rarely metastatic, the less common malignant melanoma, on the other hand, is highly aggressive and spreads rapidly to other parts of the body. Melanomas present in many different shapes, sizes and colors with a comprehensive set of warning signs.[1] 

Absolute counts by flow cytometry — maximize the accuracy of your immunophenotypic data interpretation

In this Tech Spotlight we will present the principles of absolute counting and the advantages this service provides when used in combination with tumor immunophenotypic analysis.

786-O (pMMP-LucNeo) – A model for renal cell carcinoma

Kidney cancer generally occurs in older people, with an average age of diagnosis at 64 years old. Kidney cancer is among the ten most common types of cancer in the United States, with an overall lifetime risk of approximately 1.6 percent. The most common form of kidney cancer is renal cell carcinoma (RCC), representing 90-95 percent of all cases. Unfortunately, patients are asymptomatic until advanced stage of the disease, leaving them with limited treatment options. Given the poor prognosis, which is an eight percent 5-year survival rate for patients with advanced (stage IV) disease, predictive preclinical models are needed for reliably evaluating treatment options. While subcutaneous xenograft models are valuable, they fail to capture the complexity of the cancer growing in the tissue of origin. Orthotopic models provide an avenue for not only evaluating the treatment response, but also the impact on the origin tissue and tissue microenvironment-which can be critically important in trying to preserve kidney function.

A season of gratitude and anticipation

As 2023 draws to a close, we at Labcorp thank our customers, patients, and colleagues for an incredible year. Together, we made great strides in advancing health and improving lives. This season is a time for celebration, reflection, and looking ahead. In 2024 we will continue to push the boundaries of healthcare and deliver innovative solutions that create positive change. The new year holds tremendous potential, and we can't wait to realize it together.

5TGM1-luc – A syngeneic murine model for multiple myeloma

Multiple myeloma is a malignancy of plasma B cells and is the second most common hematological malignancy in the United States. Malignant myeloma cells accumulate in the bone marrow and ultimately replace normal hematopoetic stem cells, which results in progressive leukocyte deficiencies. Chemotherapeutic agents and proteasome inhibitors are standard-of-care front line therapy that is often followed by autologous stem cell transplantation. Relapse is common with these treatment strategies,1 and research toward novel targeted therapies and immuno-therapies is being pursued aggressively.

4T1-luc2: An orthotopic mammary cancer model to support novel immuno-oncology drug discovery

Breast cancer is the second most deadly malignancy after lung cancer in woman in the United States, with an estimated 246,000 new cases and 40,450 deaths expected in 2016. Many treatment options for breast cancer exist including surgery, radiotherapy, anti-estrogen therapy, targeted therapies (e.g., trastuzumab), and chemotherapy. Despite these therapeutic advances, metastatic disease remains a significant source of mortality.

A549 – A model for non-small cell lung cancer

Today a large number of human non-small cell lung cancer cell lines exist that are being used for both basic research and drug discovery. One commonly used line is A549, an epithelial carcinoma derived from a 58 year old male patient, known to be KRAS mutant and EGFR wild type.