Cell or Sell: That Is the Question

Andrew L. Pecora, MD
Published: Friday, Sep 23, 2011
Andrew Pecora, MD

Andrew L. Pecora, MD

Editor-in-Chief

Chief Innovations Officer, Professor, and Vice President of Cancer Services

John Theurer Cancer Center at Hackensack University Medical Center

Each of us consists of some 10 to 100 trillion cells and, amazingly, we each start with a single cell. One single cell is capable of reproducing over and over, and also of differentiating (with the help of a few ham sandwiches along the way) to create an adult human able to live over 100 years. With differentiation, cells were thought to lose their ability to replicate or go back to a “de-differentiated” state. However, in vitro laboratory manipulations have shown that this is not the case. In fact, direct manipulation or indirect changes of the cell’s genetic code—read out through changes in methylation patterns or insertion of neoproteins— can render cells capable of new functions. Thus, in vitro cell manipulation has unleashed the therapeutic potential of human cells.

Recent news of the potential of cell-based therapy has garnered international attention.1 Researchers from the University of Pennsylvania published results of a gene-modified autologous T-cell therapy for advanced chronic lymphocytic leukemia (CLL). The modified T cells were engineered in vitro to express a chimeric antigen receptor that enabled the T cells to bind to a specific antigen (CD19) on the surface of CLL cells and signal other T cells to multiply and kill CLL cells. The approach resulted in a 1000-fold increase in circulating modified T cells, all capable of killing CLL cells. In the clinical trial, all 3 patients treated had dramatic reductions in their CLL burden and experienced prolonged responses. Equally compelling was the authors’ conclusion that this approach will likely be applicable to a variety of cancer types.

Another cell therapy story also made recent news, but here the emphasis was not on the cell, but the sell. Dendreon Corporation lost two-thirds of its market value after significantly downgrading its sales forecast of Provenge, a cell therapy for prostate cancer. Once equally heralded as a breakthrough therapy, the issues of limited efficacy relative to cost, reimbursement, and, according to some analysts, poor logistical execution by Dendreon management have resulted in limited utilization of Provenge to date. Dendreon has been in search of a corporate partner, but so far has been unsuccessful, which is thought by some to be due to a fundamental flaw in its business model.

On its own, with no help from scientists, clinicians, or investors, a single cell can accomplish a lot and lead to a long and healthy life. We are probably some ways off from efficiently tapping the power of cells therapeutically and commercially. Nonetheless, the ability of an autologous dendritic cell (ie, Provenge) or gene-modified T cell to significantly alter the natural history of a cancer in favor of the host is no less remarkable. Over 100 years ago people wondered what would come of tapping into the power of the atom. Just think what they will be saying 100 years from now about the power of cells.


Reference

1. Porter DL, Levine BL, Kalos M, Bagg A, June CH. Chimeric antigen receptor–modified T cells in chronic lymphoid leukemia. N Engl J Med. 2011;365:725-733. doi:10.1056/NEJMoa1103849.



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