Important Papers presented in Press Releases

The following titles are written from AACR. Oncoletter just provides the links to the official AACR website & press releases:

Cancer Aneuploidy May Predict Responses to Immunotherapy in Patients with Non-small Cell Lung Cancer

Association of aneuploidy score with clinical outcomes to immunotherapy in NSCLC

João Victor Alessi, Biagio Ricciuti, Yvonne Y. Li, et al.

Abstracts Conclusion: NSCLCs with low aneuploidy have a distinct immune microenvironment and more favorable outcomes to ICIs.



Oncolytic Herpesvirus Shows Early Promise in Pediatric Patients with High-grade Glioma

Phase I immunovirotherapytrial of oncolytic HSV-1 G207 alone or combined with radiation in pediatric high-grade glioma

Gregory K. Friedman, James M. Johnston Jr., Asim K. Bag, et al.

Abstracts Conclusion: G207 alone and combined with radiation was tolerable and safe with evidence of responses in children with pHGG. The promising median OS (12.2 mos) compares favorably with historical data (5.6 mos). Baseline HSV-1 seropositivity and seroconversion are potential biomarkers of treatment response that require further investigation. Importantly, G207 converted ‘cold’ tumors to ‘hot’ with a dramatic increase in TILs. A multi-institutional Phase II clinical trial of G207 in pHGG is forthcoming (NCT04482933).


This study will be simultaneously published in theNew England Journal of Medicine.


Bispecific CAR T-cell Therapy Shows Early Promise for Relapsed or Refractory B-cell Lymphoma

CD19/CD20 Bispecific Chimeric Antigen Receptor (CAR) in Naïve/Memory T-Cells for the Treatment of Relapsed or Refractory B-Cell Lymphomas

Sanaz Noelle Ghafouri, Christopher Walthers, Mobina Roshandell, et al.

Abstracts Conclusion: Bispecific CD19/CD20 CAR in naïve/memory T-cells are safe and effective in patients with R/R BCL. To our knowledge, this is the first study that potentially obviates the challenges of the commonest causes of relapse after CAR T-cell therapy, poor CAR-T persistence, and antigen escape mechanisms, by means of modifying naïve/memory T cells and dual antigen targeting, respectively.



Unselected Autologous Tumor Infiltrating Lymphocyte Therapy Shows Early Promise in Patients With Metastatic Melanoma

Clinical Feasibility and Treatment Outcomes with Unselected Autologous Tumor Infiltrating Lymphocyte Therapy in Patients with Advanced Cutaneous Melanoma

Robert E. Hawkins, Yizhou Jiang, Paul C. Lorigan, et al.

Abstracts Conclusion: The high response rate observed in this series exceeds the 41% ORR estimated for TIL in advanced cutaneous melanoma (meta-analysis by Dafni et al.Ann Oncol., 2019) and highlights the successful bench-to-bedside application of unselected autologous TIL to address unmet medical need in advanced melanoma. Use of tumor digests as starting material for manufacturing of TIL demonstrates feasibility of this approach. A multicenter Phase 2 trial of this therapy in advanced melanoma is planned for 2021.



Early-onset Colorectal Cancers from Patients of Different Races May Exhibit Distinct Genetic Features

Racial differences in somatic mutations among patients with early-onset colorectal cancer

Andreana N. Holowatyj, Wanqing Wen, Timothy Gibbs, et al.

Abstracts Conclusion: Together, this study provides initial evidence that molecular features of early-onset CRC may differ by race/ethnicity, which could provide insight into biological mechanisms underlying early-onset CRC disparities.



Ovarian Cancer Patients Face Increased Risk of Mental Illness

Mental health disorders among ovarian cancer survivors in a population-based cohort

Siqi Hu, David Baraghoshi, Esther Chang, et al.

Abstracts Conclusion: Higher risks of mental illnesses were observed among ovarian cancer survivors throughout the follow-up periods of 0-2 years and 2-5 years after a cancer diagnosis. Multidisciplinary care is needed to monitor and treat mental illnesses among ovarian cancer survivors.



CREB1 Identified as Potential Therapeutic Target for the Treatment of Pancreatic Cancer

Mutant p53 and oncogenic KRAS converge on CREB1 to drive pancreatic cancer metastasis

Michael Paul Kim, Xinqun Li, Jenying Deng, et al.

Abstracts Conclusion:  Our findings demonstrate a direct, mechanistic link between key oncogenic KRAS signaling elements and mutant p53 that result in a broad, multiplexed activation of cancer-associated transcriptional networks. Moreover, we identify CREB1 as a viable therapeutic strategy to undermine oncogenic KRAS and mutant p53 cooperation to mitigate PDAC metastasis.


This study will be simultaneously published in the AACR journal Cancer Discovery (PDF). The paper will be available at the following link once the embargo lifts:


Personalized Cancer Vaccine Given After Adjuvant Therapy Safe, Shows Early Efficacy in Multiple Tumor Types

An adjuvant personalized neoantigen peptide vaccine for the treatment of malignancies (PGV-001)

Thomas Urban Marron, Mansi Saxena, Nina Bhardwaj, et al.

Abstracts Conclusion: PGV-001 was successfully synthesized for 15 patients and administered successfully to 13 patients without significant adverse events. Immune monitoring of immunogenicity is ongoing, with initial analysis demonstrating induction of neoantigen-specific CD4 and CD8 T cell expansion.



Liquid Biopsy Augments MRI for Predicting Response to Neoadjuvant Treatment in Patients With Breast Cancer

Plasma cell-free DNA integrity predicts the achievement of pathological complete response to neoadjuvant chemotherapy in breast cancer patients

Gabriella Cirmena, Lorenzo Ferrando, Francesco Ravera, et al.

Abstracts Conclusion: DII measured before surgery after NACT completion shows great potential to correctly predict the achievement of pCR in BC patients. The evaluation of its use in combination with MRI is warranted in prospective studies.



Immunotherapy Response Prediction Using Tumor Mutational Burden May Differ Between Men and Women With Melanoma

The recently approved high-TMB criteria may introduce a sex bias in response to PD1 inhibitors

Neelam Sinha, Sanju Sinha, Kuoyuan Cheng, et al.

Abstracts Conclusion: The FDA-approved criteria of 10 mutations/Mb could serve as an informative biomarker for stratifying female melanoma patients but is inadequate for stratifying male patients for anti-PD1 treatment. Our results indicate that its usage is likely to introduce a sex bias in additional cancer types, which will be highly important to carefully test further in larger datasets.



News from AlphaGalileo:

The impact of chemotherapy on immune cells in the tumour microenvironment
Research from Queen Mary University of London has revealed novel insights into the effects of chemotherapy on the tumour microenvironment (TME). The study, published today in Cancer Immunology Research, a journal of the American Association for Cancer Research, found that chemotherapy enhances the anti-tumour actions of immune cells within the TME and their ability to support immune responses against cancer. SEE FULL TEXT
Implications for ovarian cancer treatment:
The results of this study along with previous findings from the team are being presented today during the poster session of the AACR Annual Meeting 2021

Chemotherapy Induces Tumor-Associated Macrophages That Aid Adaptive Immune Responses in Ovarian Cancer’

Owen Heath, Chiara Berlato, Eleni Maniati, Anissa Lakhani, Colin Pegrum, Panoraia Kotantaki, Samar Elorbany, Steffen Bohm, Simon T. Barry, Alessandro Annibaldi, Desmond P. Barton, and Frances R. Balkwill.