At Oncology Hematology Care (OHC), patients have access to multiple CAR‑T options, including Carvykti, Kymriah, Tecartus and Yescarta . These therapies reprogram a patient’s own immune cells to attack their cancer, offering new hope for individuals with aggressive blood cancers. Few regions outside major academic centers provide such a comprehensive CAR‑T program for adults.

Keytruda (pembrolizumab), one of the leading checkpoint inhibitors, is used at OHC for kidney cancer patients . Its availability here underscores the region’s commitment to delivering the most effective treatments as soon as they become standard of care.

At West Chester Hospital, a combination of Opdivo (nivolumab) and Yervoy (ipilimumab) is used as a first‑line immunotherapy for malignant pleural mesothelioma. This dual‑checkpoint approach has become a key strategy for cancers that once had few options.

Cincinnati Children’s Hospital is blazing a trail in pediatric oncology. The hospital is conducting a study of cobolimab with dostarlimab (Jemperli) for children and young adults with advanced solid tumors , aiming to establish safe dosing and expand the benefits of immunotherapy to younger patients.

These initiatives reflect a collaborative ecosystem of hospitals, research centers and specialists who are not just adopting but actively shaping the latest advances. Cincinnati provides patients with access to treatments that harness the power of the immune system and genetic engineering, and it offers healthcare professionals the opportunity to participate in pioneering clinical research. In short, the city is evolving into a true treatment hub for cancer innovation.

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They transformed hematologic cancers. Can they do the same in solid tumors?

Bispecific antibodies have already proven their value in hematologic malignancies. Agents like blinatumomab validated the concept of redirecting T cells toward tumor cells by simultaneously engaging CD3 on T cells and a tumor-associated antigen. However, replicating that success in solid tumors has proven far more difficult. Physical barriers, antigen variability, and immunosuppressive microenvironments pose substantial challenges.

Still, the field is moving forward. A new generation of bispecifics is entering clinical development, engineered specifically to overcome the limitations of solid tumors.

From Blood Cancers to Solid Tumors: The Shift Begins

The first wave of bispecific T cell engagers, particularly blinatumomab, demonstrated that CD3-directed immune redirection could induce durable responses in B-cell acute lymphoblastic leukemia. That success launched a wave of research, but much of it remained focused on blood cancers where immune effector cells have easier access to tumor cells.

In solid tumors, the biology is more complex. Tumor heterogeneity, limited T cell infiltration, and the potential for on-target, off-tumor toxicity have slowed progress. Despite these challenges, drug developers are refining antibody design to bring this modality to solid tumors.

Challenges Unique to Solid Tumors

Developing bispecific antibodies for solid tumors presents a fundamentally different set of obstacles than in hematology.

• Antigen specificity is more difficult to achieve. Solid tumors often express targetable antigens at lower levels, and sometimes on healthy tissue as well.

• The tumor microenvironment can limit immune activity. High levels of immunosuppressive cells and cytokines often inhibit the function of redirected T cells.

• Pharmacokinetics and half-life also matter. Many early bispecifics required continuous infusion due to their short duration in circulation, complicating patient management.

• Safety concerns arise when tumor antigens are also expressed on normal tissue, increasing the risk of cytokine release syndrome or other immune-mediated toxicities.

New Engineering, New Strategies

Drug developers are addressing these limitations through more sophisticated engineering approaches. Several notable bispecifics are now advancing through early and mid-stage trials in solid tumors.

• Tarlatamab, developed by Amgen, targets DLL3 and CD3, and is being studied in small cell lung cancer.

• Claudin 18.2-targeting bispecifics are under investigation for use in gastrointestinal cancers.

• Masked bispecifics, which remain inactive until they encounter tumor-specific enzymes, are being developed to improve safety.

• Alternative cell engagers, including bispecifics that engage NK cells rather than T cells, are also in early trials.

These approaches may offer improved selectivity, more favorable pharmacokinetics, and better tolerability.

What to Watch Going Forward

The success of bispecifics in solid tumors will depend on several factors.

• Identifying tumor-specific or tumor-enriched antigens remains a top priority.

• Improving the immune contexture of cold tumors through combination strategies may help bispecifics achieve efficacy.

• Advances in antibody formats that prolong half-life and improve tumor penetration will likely be essential for broad clinical impact.

The field is watching closely to see which design strategies translate into durable clinical responses. Early signals are promising, but large-scale validation is still needed.

Closing Thoughts

Bispecific antibodies have already demonstrated their therapeutic value in hematologic cancers. The question is whether these molecules can be adapted to overcome the distinct barriers posed by solid tumors. As clinical trials continue and new designs emerge, bispecifics may yet play a central role in the next wave of solid tumor immunotherapy.

If you are following this space or working on related projects, I would be interested in hearing your perspectives. You can reach out directly or join the conversation below.

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DeepHRD: Detecting homologous recombination deficiency from histology

Some breast and ovarian tumors carry a condition called homologous recombination deficiency (HRD). HRD prevents cancer cells from repairing DNA damage, making them especially sensitive to platinum chemotherapy and PARP inhibitors. Traditional HRD assays rely on next‑generation sequencing of the tumor’s DNA and often come back inconclusive or require repeat biopsies . DeepHRD offers an alternative. Researchers from the University of California San Diego trained this deep‑learning model on digital images of more than 1,000 breast‑cancer and 459 ovarian‑cancer slides . The system uses a multiresolution approach similar to how pathologists examine slides under different magnifications, but it picks up subtle structural changes that the human eye cannot see . In a study published in May 2025, the DeepHRD test had a negligible failure rate compared with the 20–30 % failure rate seen with standard genomic tests . That means clinicians can get a reliable result from the initial biopsy and begin treatment sooner.

DeepHRD’s performance also exceeds existing molecular tests. In an analysis of breast and ovarian cancer cohorts, DeepHRD achieved an area under the curve (AUC) of 0.81 when predicting HRD status . The model identified 1.8 to 3.1 times more HRD‑positive patients than standard tests . Those patients showed better overall survival in high‑grade serous ovarian cancer and a 3.7‑fold increase in median progression‑free survival (14.4 vs 3.9 months) when treated with platinum chemotherapy . Because DeepHRD analyzes digitized slides, the results are available almost immediately after the biopsy . It reduces the need for expensive sequencing, expands access beyond major cancer centers and integrates pathologists more directly into precision oncology .

MSI‑SEER: Visualizing microsatellite instability to guide immunotherapy

Microsatellite instability‑high (MSI‑H) status is another biomarker that guides targeted treatment, especially immunotherapy. Conventional MSI tests produce a binary result and may miss focal regions of MSI‑H within a tumor. Vanderbilt University Medical Center and collaborators developed MSI‑SEER, a weakly supervised deep‑learning model that predicts MSI‑H status from standard hematoxylin‑ and eosin‑stained slides . The tool divides each slide into thousands of tiles and calculates region‑by‑region probabilities of MSI‑H, allowing clinicians to see heterogeneity across the tumor . In several cases, MSI‑SEER identified MSI‑H regions in tumors previously labeled microsatellite stable; those patients subsequently responded to immunotherapy . A key innovation of MSI‑SEER is that it reports both the predicted status and its confidence, giving oncologists a measure of reliability . By combining AI‑generated insights with physician judgment, MSI‑SEER helps ensure that patients who might benefit from checkpoint inhibitors are not overlooked.

A broader shift toward AI‑driven precision medicine

DeepHRD and MSI‑SEER are part of a broader trend in oncology toward algorithms that read images rather than waiting for sequencing. At UCSD, researchers emphasize that DeepHRD’s image‑based analysis can resolve ambiguous cases where genomic tests fail. Vanderbilt’s team describes MSI‑SEER as a way to visualize tumor heterogeneity and to identify patients with low or heterogeneous MSI features who may still respond to immunotherapy . These tools reduce the cost and turnaround time of biomarker testing, potentially making precision treatments more accessible . Although AI models can harbor biases if trained on limited populations, researchers believe their accessibility will improve data collection across diverse ethnicities .

Other AI‑driven tools are emerging as well. Google Health’s research team is developing an AI system to interpret mammograms; early results suggest that it can detect breast cancer as accurately as radiologists . The combination of deep learning and medical imaging is already speeding up diagnoses across specialties.

Looking ahead

AI tools like DeepHRD and MSI‑SEER show that histopathology slides contain far more information than the human eye can extract. By training models on large, diverse datasets, researchers have created algorithms that not only detect genetic defects but also provide interpretable insights and confidence measures. These advances are allowing clinicians to start targeted therapies earlier and to identify patients who would otherwise be missed. As more data becomes available and algorithms mature, AI‑driven diagnostics may become a routine part of the cancer care pathway, bringing precision medicine closer to the point of diagnosis for patients around the world.

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What is BiTE Therapy? BiTE therapy is a form of targeted immunotherapy that uses engineered antibodies to direct the body's own T-cells to attack cancer cells. A BiTE molecule is a synthetic protein with two arms. One arm binds to a specific antigen on cancer cells (like CD19), and the other binds to CD3, a receptor on T-cells. This connection brings the T-cell in close proximity to the cancer cell, allowing it to release cytotoxic granules and kill the target cell.

Unlike CAR-T therapies, BiTE therapies do not require genetic modification or cell harvesting. They are off-the-shelf biologics that can be administered immediately, often as continuous intravenous infusions.

Advantages of BiTE Therapy

• Off-the-shelf convenience: Unlike CAR-T cell therapy, BiTEs are ready-made and do not require complex lab procedures.

• Rapid onset: Since they do not rely on patient-specific cells, treatment can begin much faster.

• Repeat dosing: BiTE therapies can be administered in multiple cycles, providing ongoing engagement with the immune system.

• Broad development potential: Researchers are exploring BiTE therapies for various targets beyond CD19, including solid tumors.

Current and Future Applications The most well-known BiTE therapy is blinatumomab (Blincyto), approved for B-cell ALL. However, the pipeline includes therapies targeting BCMA in multiple myeloma and EpCAM in epithelial cancers. Future generations aim to increase tumor selectivity and reduce cytokine release syndrome (CRS).

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The discussion also explores common complications such as graft-versus-host disease (GvHD), infections, and organ toxicity, along with emerging strategies to manage them. With emphasis on long-term survivorship and quality of life, the episode brings attention to how advancements in HCT are reshaping standards of care. Whether you're a healthcare professional or a curious listener, this episode simplifies the complexities of transplant medicine into digestible insights.

Handbook can be found at https://www.ebmt.org/education/ebmt-handbook

Here’s a breakdown of how they compare.

Chemotherapy: The Traditional Approach

Chemotherapy uses strong drugs to kill fast-dividing cells. This includes cancer cells, but also healthy ones like those in hair follicles, bone marrow, and the digestive system. That’s why side effects can be so tough.

• Benefits: Works for many cancer types and is widely available

• Drawbacks: Non-specific targeting and heavy side effects

• Common use: Often used in solid tumors like breast, colon, and lung cancer

CAR-T Therapy: Personalized and Powerful

CAR-T stands for Chimeric Antigen Receptor T-cell therapy. Doctors collect your T cells, reprogram them to recognize cancer, and then infuse them back into your body. It’s one of the most exciting advances in cancer care.

• Benefits: Can lead to remission in difficult cases like relapsed lymphoma or leukemia

• Drawbacks: Complex, costly, and can cause serious immune reactions

• Common use: Approved for certain blood cancers that have not responded to other treatments

BiTE Therapy: The Connector

BiTE stands for Bispecific T-cell Engager. These are engineered molecules that bring your own T cells into direct contact with cancer cells so they can destroy them. Unlike CAR-T, this therapy doesn’t require modifying your own cells.

• Benefits: Off-the-shelf availability and a quicker turnaround

• Drawbacks: Short half-life, often requires continuous IV infusion

• Common use: Used in acute lymphoblastic leukemia and being studied in other blood cancers

The Big Picture

Chemotherapy remains essential in many cases, but it is no longer the only option. CAR-T and BiTE therapies offer more targeted, immune-driven solutions that are already saving lives. As research grows, these treatments may become more common, more affordable, and possibly more effective in a broader range of cancers.

With a background in cell and molecular biology, I find this shift encouraging. These therapies show us that we are not just treating cancer, we are learning how to turn the body’s own defenses into precision tools.

Let’s talk about it.

What have your experiences been with these therapies? Comment below or send me a message. I’d love to hear your story or questions.

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