By: Teisha Rowland, Ph.D., Principal Scientist
Last fall, I felt a lump in my breast. After debating for a few days about what to do – Had it been there before, and I just hadn’t noticed it? Should I be concerned about it? – I ended up calling my Obstetrics and Gynecology (OBGYN) physician’s office. They encouraged me to get it checked out and managed to get me an appointment for a few weeks later. Waiting was suspenseful and stressful. I thought of my mother-in-law, who died of breast cancer in 2014, and my own mother, who is a breast cancer survivor. Fortunately, after a quick examination, my OBGYN found everything to be normal.
For many women, their story has a different ending. Breast cancer can present itself as a lump in the tissue that is usually painless1, making it easy to be ignored. Other symptoms include tissue thickening or a change in the shape or appearance of the nipple or breast (which may involve dimpling or redness or other skin changes, or an unusual nipple discharge). Even if symptoms are painless – which malignant lumps typically are – it is highly recommended that someone with any of these symptoms quickly visit a physician within 1 to 2 months of symptom onset for an examination. Early detection is crucial for having the most successful treatment and outcome.
Worldwide, breast cancer is the most common cancer type, and there are more cases of breast cancer diagnosed than any other cancer type. In 2020, there were more than 2.3 million new cases, and 685,000 people died1,2. If cases progress along their current trajectory, it’s predicted that by 2040, there will be more than 3 million new cases and 1 million deaths annually2.
Available options to treat breast cancer have evolved over the years from primarily invasive options such as complete breast removal to more current treatment options, including radiotherapy, chemotherapy, less invasive surgery options (such as partial mastectomy, or lumpectomy) and targeted breast cancer immunotherapies. The first immunotherapy drug approved by the FDA (in the 1990s) for breast cancer was Herceptin (trastuzumab), developed by Genentech. Herceptin is a monoclonal antibody that targets HER2, a cancer biomarker expressed by ≈20-30% of early-stage breast cancers. A cancer biomarker is typically a surface protein that is more highly expressed in certain cancer types compared to healthy cells, allowing targeted treatment of cancer cells specifically.
Today, treatments for breast cancer can be highly effective, especially if diagnosed early, with probabilities of patient survival for ≥5 years reaching ≥90% in high-income countries1. However, survival rates are decreased in lower-income countries with limited resources, dropping to 66% in India and 40% in South Africa1. If the diagnosis does not occur early, survival rates decrease. There is still a need to develop new and innovative targeted therapies that improve long-term survival, decrease cost, and increase accessibility worldwide to help overcome many of the major challenges we still face today to successfully treat people with breast cancer.
To bypass adverse effects of conventional chemotherapy that can leave patients feeling very sick and unable to complete treatment, more targeted immunotherapy approaches are being pursued. One such promising cancer biomarker is the folate receptor (FR). FR is expressed in many different cancer types, including breast cancers3. In particular, FR expression is relatively increased in estrogen receptor (ER)/progesterone receptor (PR) negative and triple-negative breast cancer (≈15-20% of patients), a devastating subtype that carries a relatively poor prognosis3,4.
New technologies are offering hope for these hard-to-treat cancers and at Umoja Biopharma, we announced in May 2022 the Seattle Children’s activation of the Phase 1 ENLIGHTen clinical trial, which is targeting FR in cancer patients. This trial uses chimeric antigen receptor T-cell (CAR-T) therapy, which uses the patient’s own T-cells that are reprogrammed to recognize and kill cancer cells, along with a TumorTag , Umoja’s proprietary small molecule that targets tumor biomarkers. Specifically, this TumorTag (UB-TT170) selectively binds to FR on tumor cells, labels them with fluorescein, and marks them for destruction by specially-designed CAR T cells. While a significant challenge in the immunotherapy field is the unpredictable efficacy of treating solid tumors such as breast cancer due to the hostile tumor microenvironments and tumor heterogeneity, Umoja’s TumorTag platform aims to improve efficacy by labeling multiple targets in the tumor environment with a cocktail of TumorTags. UB-TT170 and other TumorTags are also used in Umoja’s upcoming therapeutic candidate, UB-VV200, with an IND submission being targeted as soon as 2024.
While the Phase 1 ENLIGHTen clinical trial is assessing safety and tolerability in patients with osteosarcoma, it is paving the way for targeted therapies for other cancers where FR is overexpressed, such as the triple-negative breast cancer subtype. One of the limitations of current CAR T therapies on the market is the need for lymphodepleting chemotherapy, which can be toxic and leave patients feeling too sick to complete treatment. To address this, Umoja has developed another approach that uses our Rapamycin-Activated Cytokine Receptor (RACR) platform to selectively enrich and expand engineered CAR T cells inside a patient’s body and enhance the anti-tumor response. Umoja recently published on the RACR technology in Journal for ImmunoTherapy of Cancer.
While breast cancer treatments – especially when the cancer is caught early – can be highly effective, challenges remain in developing treatments with fewer adverse side effects and improved affordability and accessibility. By overcoming such challenges, new therapies offer hope to the millions of people diagnosed with breast cancer each year.